Founder's Site

James E. Summerton, Ph.D.

Founders-Site.Onco-Tools.com

[9] Amanda’s Cancer: Hope for the Hopeless

[ link 9 ]

AMANDA’S CANCER:

Hope for the Hopeless

[This story, set in 2020, describes what we believe
will soon be the treatment of choice for all cancers.]

James Summerton, Ph.D. and Donald Moss, Ph.D.

27 August 2017

“Hey, did you get the word problem about the train going west at 70 miles per hour and a boat going south at 15 knots, how fast is the train moving away from the boat ?” Amanda asked as she and Sylvia trooped into their advanced placement eighth grade math class. Sylvia rolled her eyes and shook her head as they slid into their seats.

Amanda and Sylvia didn’t fit the hotsy-totsy in-group. When she’d gotten her glasses, she’d thought they were cool, made her look serious. But the lenses made her eyes look big and the other kids called her “Googley.” She could tolerate the name-calling because Sylvia also wore thick glasses and they both dressed in old jeans and sweatshirts. The two girls competed with each other, and generally got at least five points higher than the other three kids on the Advanced Placement math tests.

Amanda and Sylvia had only three months left to prepare for the Spring of 2020 Kansas state-wide math contest. They hoped to be selected to represent the Cottonwood Springs Independent School District and it would take some hard work. The other twenty three kids in the eighth grade, the ones not included in the advanced placement group, made fun of the “nerd birds”. Did Kansas farm kids think they could run a modern wheat farm without math?

Amanda had come up with an answer about the train and the boat, but doubted that anyone else got it right. In fact, learning that the problem had stumped her friend Sylvia, Amanda now had less confidence in her own solution.

The night before, when Amanda had finished milking the family cow and feeding her sheep, Mikey, her fifth grade brother, had told her that he needed help with his spelling words. She couldn’t say no, although she could have used the extra hour of checking her work on the train and boat problem. But she loved the way Mikey looked up to her, wide eyed, when she proved over and over again that she knew everything in the world, at least from his fifth grade point of view. She smiled when she thought of Mikey, a kid small for his age with curly red hair, and how they laughed together at his clumsy attempts to master the mysteries of English spelling.

Amanda’s thoughts of Mikey and his spelling words were interrupted when the teacher asked everyone to pass in their homework. The teacher started up his computer and after a few moments of whirring, it flashed the new problem for the day on the screen.

Even with her coke-bottle glasses pushed up on her nose, the letters on the screen slipped back and forth like they were riding waves, overlapping each other. That had started happening more and more often over the past couple of months. This time, the fuzzy letters made Amanda feel dizzy. And the heat of the room combined with something from the school lunch made her stomach began to rebel. Amanda felt like she might throw up on the spot. She swallowed hard, leaned over and whispered in Sylvia’s ear, “I’ve got to go.”

Amanda felt all the students turn to watch her, their eyes drilling into her back as she dashed for the door. The bathroom door slammed the wall behind her as she stepped up to the basin, gripping it with white knuckles, and began retching. Tears ran down her cheeks. She bit her lip as a wave of pain seared her insides like a hot iron. This attack was worse than any she’d had since they had started a few weeks earlier. Those had passed within a few minutes. Maybe this one would, too. Holding her breath, her agony lessened to waves of nausea.

Still leaning on the sink, Amanda let herself collapse forward so her forehead rested against the cool mirror. She took two deep breaths before her stomach begin to cramp. Fighting dizziness and swallowing vomit, Amanda rushed into a stall and plopped herself onto a stool. After a few minutes, she got up, pulled the handle, and watched blood stained water swirl down the hole.

The sight of the blood scared her. She’d never seen that before. Her skin felt cold. It wasn’t supposed to be like this, so painful. Amanda began to sob.

* * *

When Amanda finished peeing in the clear plastic cup, she held it up to the light and saw it was red and cloudy and bloody. She’d gritted her teeth when the lab technician had jabbed a needle into her arm and she’d watched her blood bubble up into a glass tube. Now it was time for Dr. Gibson to poke her like a piece of meat.

The white paper gown, open in the back, did nothing to keep the cold steel table from her bare skin. Another attack the previous day, this one at home, had scared her mother into making an appointment with Dr. Gibson, the doctor who had taken care of Amanda since she was three. Now Amanda found blood in her urine all the time.

Dr. Gibson smiled and pushed her gloved fingers into the soft area below Amanda’s ribs. “Does this hurt?”

Amanda shook her head in a silent no.

“How about here?” The older woman’s fingers crossed, and then re-crossed, the same place on Amanda’s lower right side. “Hmmm, what do we have here?” her smile faded.

“What’d you find?” Panic bubbling up inside. A fear of something serious had been nagging at her for weeks.

“A hard spot…, right here.” Dr. Gibson guided Amanda’s fingers over a lump in the soft part of her belly. “I’m going to send you to get an X-ray, see what that is.”

An hour later, back in Dr. Gibson’s office, she pointed to a computer screen showing Amanda’s insides. “That round area about the size of a golf ball shouldn’t be there.” Dr. Gibson’s eyes looked kind but her lips had pursed, showing extra wrinkles. “This is probably the cause of your pain and the blood in your urine.”

“How long has that been inside of me?” Amanda shifted in her chair to get a better view of the computer screen. “Why haven’t I felt it before? What is it ?

“We will have to find out. First of all, however, Amanda, have you had any other problems? Anything else you need to tell me?”

Amanda rubbed her forehead for a few moments. “I feel like I need to throw up a lot.” She paused. Dr. Gibson waited. “And sometimes I can’t get my eyes to work right, everything gets fuzzy. It’s getting worse.”

Dr. Gibson scribbled some notes before she looked up and took Amanda’s chin in her left hand. She then focused a bright light into one of Amanda’s eyes, then alternated from left to right eyes and back again. The black center of Amanda’s left eye jumped to different sizes as the light came and went. The right eye didn’t change. “Hmmm. We’ll have to run some tests to know for sure.”

* * *

Since her appointment with Dr. Gibson a week earlier, Amanda had endured three more attacks, and she’d been through dozens of tests. Now she suffered in silent panic as her mother drove the 15 miles to the clinic for the results. She tried to concentrate on the trees, or anything interesting she could find along the way, to keep her mind busy. Nothing worked. Everything looked fuzzy.

Dr. Gibson met them at the front door and ushered them into her office and asked them to sit at a table facing a screen on the wall. She took a seat next to Amanda, took her hand, and spoke to her in a soft voice. “I am going to go through everything we’ve found and then we’ll talk about what it means. Stop me, however, if you have a question.” With that, Dr. Gibson dimmed the lights and turned on the slides.

The pictures flashed, one after another, on the screen. Amanda couldn’t read the words or make out the details. One image showed the golf ball sized circle in Amanda’s insides that she’d seen before. Dr. Gibson stood and pointed to different spots in the grainy black and white images with a pointer. After a parade of photos explained with words like “abnormal”, “mass”, “lump”, and “afraid it has spread”. Dr. Gibson stopped and the screen went dark.

 

TRAGEDY: “Amanda,” Dr. Gibson walked back over and took her seat next to her young patient, “the cause of the lump and pain in your abdomen, as well as the blood in your urine, is that you have cancer in your right kidney.”

Dr. Gibson blinked back tears as she looked hard into Amanda’s eyes. “Because you have been feeling like you need to throw up and your eyesight has been bothering you, I also ordered the scans of your brain. These show that there are three tumors, each about the size of a marble, in the lower part of your brain. There are several others which are smaller. However, these cause pressure and make you feel like throwing up. One of those is also pressing on the nerve that goes to your right eye. I am afraid the cancer from your kidney has spread to your brain.”

Dr. Gibson wiped her eyes and blew her nose before she went on. “Because it has spread to your brain, I also had you come in for a whole body scan, looking for other places the cancer may have spread to. Your bones also show hot spots.”

Amanda and her mother sat in stunned silence for a full minute before Amanda’s mother spoke. “What are the treatment options, Dr. Gibson ? These are treatable, aren’t they ?” Her voice cracked and tears began streaming down her cheeks. A stifled moan escaped Amanda’s lips.

 

ALL HOPE IS LOST: “Sometimes, if the cancer is caught early enough, it can be treated with surgery, radiation, especially for tumors in the brain, and chemotherapy. And, of course, we can discuss those options and come up with a plan. Unfortunately, however, in this case, we didn’t catch it early. At this point, especially after cancer has spread to the bones, it is very difficult to treat and unlikely we can be successful.”

Amanda collapsed into her mother’s arms and started sobbing uncontrollably. “I’m going to die ?

Dr. Gibson reached over and touched Amanda’s shoulder. “I’ll set up an appointment with Dr. DeVita, a cancer specialist. We’ll see what can be done.”

* * *

The following Tuesday, Amanda found herself waiting alone in a doctor’s office amid rows of books. She stood at the window behind the doctor’s desk and looked out over an expanse of parking lots and trees. At that moment, her mother and Dr. DeVita had stepped into the hall. How many months did she have to live and how much pain would she suffer before she died ? She feared an awful death awaited her. Amanda leaned against the window glass and cried. She felt it was hopeless. She’d lost all hope.

After several more long agonizing minutes, the doctor, a gray-haired man with black bushy eyebrows, opened the door for Amanda’s mother and then followed her into his office. He had kind brown eyes, a ready smile, and wore a cologne that smelled like leather. For a moment, Amanda thought about the times she and Mikey rode horses. She felt better and liked the older man who reminded her of her grandfather.

Dr. DeVita motioned to some chairs arranged around a cluttered wooden table off to the side of his desk. “Amanda, you’re a bright fourteen-year-old who should have a say in what we do. Would you like to sit down and help us figure out what we’re going to do ?

Dr. DeVita moved some colorful models of the insides of people and a stack of papers off the table. He closed a thick book and sat down across from Amanda and her mother. “Your mother tells me to be direct, tell it like it is. Is that what you want ?

Amanda nodded. Words would not squeeze by the lump in her throat.

                        

CONVENTIONAL CANCER TREATMENTS:
“Then that’s what we’ll all do, be frank, tell each other the truth. So I am going to start out by telling you about conventional cancer treatments approved by the US Food and Drug Administration (FDA).”

 “Fifty years ago only about 30% of cancer patients survived their cancer – with survival being primarily due to surgical removal of early-stage cancers. However, by 2016 about 67% of cancers could be cured – with much of that improvement coming from high-dose treatments with cocktails of two or three chemotherapy drugs. While those harsh treatments with cocktails of high-dose chemotherapy drugs devastate patients, the payoff is that far more patients are actually cured than earlier when only a single chemotherapy drug was used at a moderate dose. Of particular note, the harsh treatments with cocktails of high-dose chemotherapy drugs provide sharply increased numbers of cures even when the patients’ cancers have spread to multiple organs – where 50 years ago such spread had been a near-certain death sentence [1].”

“Improvements in detection of cancers have also contributed to the slowly increasing average cure rates by allowing treatments to begin sooner. Also, the technology for treatment with focused high energy beams has been continually improving. Still other improvements have been achieved by targeting some cancer types with radioisotopes bound to monoclonal antibodies which specifically bind to certain cell surface structures that are present at substantially higher concentrations on cells of certain cancer types relative to the patient’s normal cells. And quite recently, a new class of anticancer agents, called “checkpoint inhibitors” have provided another mode of attack on some cancer types which have mutations that allow the cancers to evade or suppress the patient’s normal immunological defenses against cancers. Checkpoint inhibitors overcome the cancer’s evasion of the patient’s immune defenses. However, these checkpoint inhibitors can sometimes stimulate the patient’s immune system to attack and destroy normal organs of the patient – with dire results for the patient.”

“Also promising is a drug Gleevec, taken one pill a day, which can be used to block a specific cancer indefinitely. That drug targets a protein resulting from a chromosomal fusion unique to the specific cancer and essential for the growth of that specific cancer. While Gleevec is not a cure, it does save the patients’ lives as long as they continue to take the drug. However, while it is a simple drug, it is very expensive and needs to be taken every day for the rest of the patient’s life, making it a serious financial strain on health care systems. It also causes a variety of side effects in some patients.”

“While the cure rate for cancers has more than doubled over the past 50 years (going from about 30% to the current 67%), with cure rates for a few cancer types being in the 80% to 99% range, it should be appreciated that there are still a substantial number of cancer types where the cure rates are only in the range of 3% (for pancreatic cancer) to 33%. Furthermore, with many of the current conventional cancer therapies, even when the patient’s cancer is cured, serious long-term side effects from the treatment can persist – sometimes for the rest of the person’s life.”

“Now with regard to your cancer, I am going to start out by telling you that conventional treatments, approved by the FDA, offer little hope. Of course, we could use surgery to take out your right kidney and you could undergo radiation and chemotherapy for the tumors in your brain, bones, and wherever the cancer might be hiding. I could give you pain medicine to help with the pain, and radiation therapy is effective in reducing the grinding cancer pain in bones, even though it cannot cure it. During the chemotherapy you would lose your hair and often be miserable with nausea, vomiting, and diarrhea.”

“However, because your cancer is a very rare type which oncologists have little experience in treating, and because your cancer is at such an advanced stage and has spread throughout your body, with such conventional cancer treatments you would likely have only a small chance of living even a year.”

“The problem is that no one has devised an effective conventional treatment for the rare type of cancer you have. In fact, no one’s even looking for a way to cure your type of cancer. There are only about 50 cases of this type of childhood cancer a year. It’s all about money. Drug companies can’t spend millions of dollars to develop a new drug for a rare cancer, and then spend hundreds of millions of dollars to test it on thousands of people in order to get regulatory approval – all to treat only a handful of patients. And most of the time the first three or four drugs they develop don’t work. For rare diseases the drug companies often spend hundreds of millions of dollars for testing each drug they develop, and the patients generally die anyway, often sooner, sometimes later.”

Amanda’s mother pulled her chair over to Amanda, put her arm around Amanda’s shoulder and gave her a hug. Amanda snuggled up to her mother and felt a little better.

NEW HOPE: Dr. DeVita reached across the table and took Amanda’s hand. The lines in his face softened a bit and he took a deep breath. She had a feeling something very important weighed on the doctor’s mind. Words escaped her. She simply nodded.

Dr. DeVita began. “Amanda, I’ve given you the bad news first. Now I want to tell you about a new unconventional and controversial cancer treatment that is rocking the oncology field. That treatment is controversial because it has not undergone the conventional three phases of clinical testing previously requiredby our government’s drug regulatory agency, the FDA. In spite of that controversy, I want you and your mother to know about this new treatment option, and I want to explain it to you in enough detail that you understand what is involved so you can make an informed decision on whether or not you want to try it.”

“What if we had a treatment developed specifically for you, which almost always works to cure your specific cancer, and you would be fully recovered within a few months, without surgery, or radiation, or the misery and suffering of chemotherapy, and without the risk of serious long-term side effects from the treatment plaguing you perhaps the rest of your life ?

Amanda’s mother sat up. “Is that possible? Or would it just be using my daughter as a guinea pig in a clinical trial – with only a 50-50 chance of even getting the new drug ?

Dr. DeVita faced Amanda and the distraught woman cradling her. “It’s not a clinical trial. It is a new personalized therapy strategy for treating cancers which uses a custom cocktail of precision-targeted drugs [2], called Morpholinos. Each Morpholino [3] of the cocktail will block or modify a selected target structure essential to Amanda’s cancer – without harm to Amanda. Amanda is a perfect candidate for such a therapy.”

Amanda looked up in confusion. “How would it work?”

Dr. DeVita began to explain. “It’s rather complicated, but here goes. In each of your cells tens of thousands of genes, which are made of DNA, contain the information for making and operating your body. That information is carried from the DNA to the rest of the cell by RNA transcripts, which are copied directly from the DNA of the genes. Those transcripts then code for the assembly of proteins, as well as carrying out other functions of the cell. Information in your genes, and their transcripts which carry that information throughout the cell, determined the color of your eyes, make you tall or short, male or female, and everything about each person. They provided the information to make your brain, muscle, liver, kidneys, and skin.”

“Most of these structures were made when you were still in your mother’s womb and then many of the genes responsible were turned off before you were born, while others continued to function after you were born, and some are turned on only after birth, such as when you reach puberty or when a woman becomes pregnant. All these structures, made before you were born and maintained throughout life, must work together in a controlled manner for you to function normally.”

“Cancers generally start in one of your cells when a critical gene is mutated, or when a cell is infected with a cancer-causing virus. However, for a full-blown cancer to develop, multiple additional mutations must occur in other key genes of that cell – and each of those random mutation events can take additional years to decades to occur. That is why cancers are so rare in children, but become much more common as we grow older. When enough mutations accumulate in key genes in a cell, that cell can escape from the finely-tuned controls that keep cells functioning for the good of the person. This can result in the new cancer cell undergoing rapid growth and division and allow its progeny cells to invade other tissues, as well as usurp so much of the body’s resources and processes that it finally destroys the person.”

Dr. DeVita continued, “In your case, Amanda, some of your genes, likely including a number of genes which were turned off before birth, but then turned back on by mutation to form your cancer (called oncofetal genes), are running amok, wrongly telling your body to make new kidneys. The hard mass in the soft part of your belly is a new kidney being assembled. But you don’t need it. Not only are you getting a kidney you don’t need, the growth is running wild, raging out of control, and the new kidney cells are migrating into your blood stream and going to other parts of your body. This is how cancers spread. Often where they land they blindly start building a new kidney without any controls. The tumors in your brain, bones, and everywhere in your body are little colonies of cancerous kidney tissue reproducing themselves as fast as they can. That damages good parts of your body, steals energy, makes you sick, and, if left untreated, would soon kill you.”

Amanda asked “Can these genes be stopped ? Can my cancer be cured this way ?

 

TREATMENT CHALLENGES: Dr. DeVita responded. “Before answering your question I’d like to give you an idea of what we are up against when treating cancers. Each patient’s cancer evolved from the patient’s normal cells and so both normal and cancer cells contain nearly all the same genes and proteins. Therefore, a central challenge in treating cancers is to completely destroy all of the cancer cells without also seriously damaging or killing the nearly identical normal cells of the patient.”

“Also, each patient’s cancer has evolved via multiple random mutations over the course of years to decades. As a result, virtually every patient’s cancer differs from every other patient’s cancer in regard to which genes are turned on and off. Thus, the other major challenge in treating cancers is to safely and reliably cure any patient’s cancer – in spite of these often wide-ranging and unpredictable differences between cancers.”

                  

A NEW ERA IN CANCER TREATMENT:
Dr. DeVita continued. “Once these treatment challenges are understood, it becomes fairly obvious what needs to be done to reliably cure any patient’s cancer without harming the patient – that being to identify multiple structures which: (i) are absent from the patient’s normal cells; but (ii) are present in or on that particular patient’s cancer cells; and, (iii) are essential for the viability of those cancer cells. After identifying such cancer-essential structures, the next step is to treat that patient with a custom cocktail of drugs which selectively inactivate multiple cancer-essential structures in the patient’s cancer. Cancer-essential structures constitute ideal therapeutic targets because they can be completely blocked to kill the cancer, without harming any of the patient’s normal cells.”

“While it is obvious what needs to be done to cure any patient’s cancer, it is far less obvious how to achieve such a highly selective attack on multiple cancer-essential structures in a given patient’s cancer in a timely, affordable, and practical manner.”

Since the goal is to cure virtually any cancer in any patient, and to do so affordably, it is important to pick a suitable class of cancer-essential structures which can be rapidly and affordably identified in any patient’s cancer, and which can be specifically targeted with a cocktail of easy-to-design and affordable-to-produce drugs.”

“With recent advances in several different technologies, the long-sought goal of being able to cure any cancer in any patient has finally been achieved with a new custom cancer treatment strategy [2] – called a “Custom Cocktail for Curing Cancer”, or 4C.”

“The general class of structures targeted in this 4Cstrategy are RNA transcripts absent from normal adult cells, and present only in the cancer. These cancer-only transcripts are important because many of the genes used to build your body while you were in your mother’s womb, and then turned off before you were born, are just the genes that get turned back on by mutations, and then become cancers because they can outgrow normal cells. Because those genes which have been turned back on in your cancer (oncofetal genes) are not needed in your normal cells after birth, but are present in your cancer, the RNA transcripts of those oncofetal genes can be thoroughly blocked or altered without harm to the patient.

However, it turns out that many of those cancer-only RNA transcripts from oncofetal genes, and oncogenic viral genes, though present in the cancer, are not essential for the viability of that cancer.”

“Thus, a second key step is needed to identify just the special subset of cancer-only transcripts which are essential for the viability of the cancer. Most transcripts in this special subset of cancer-only transcripts, called cancer-essential transcripts, were identified in 2017 and 2018 by a consortium of cancer research groups around the world. This entailed blocking, both one at a time and in combinations, each of a large number of cancer-only transcripts from a wide variety of cultured human cancers to determine which blockages caused the death of the cultured cancer cells. The special tools used for that project were high-specificity transcript-blocking “Onco-Morpholinos[4], developed by Dr. Summerton [5, 6] in Oregon, and in early 2017 made commercially available to the cancer research community by Onco-Tools, LLC.”

“In 2018 that project by multiple cancer research groups provided a master list of most of thecancer-essential transcripts in human cancers. That 2018 master list, with references to the published research, is available for free on the internet.”

“To start such a treatment, the transcripts from a biopsy sample of your specific cancer must be identified. A computer then uses that 2018 master list of cancer-essential transcripts to identify which of the identified transcripts in your cancer are suitable for targeting. With that information, a set of appropriate transcript-blocking drugs are assembled into your custom cocktail to be used for treating your cancer – without harm to your normal cells.”

“Even after your cancer has spread throughout your body, complete eradication of your cancer, without harm to you, can almost always be achieved by using a custom cocktail containing multiple different transcript-blocking Morpholinos, where each different Morpholino of your cocktail targets a different cancer-essential transcript, which was identified from your biopsy sample as being present in and essential for the viability of your cancer.”

“Now to answer your questions: Can these genes be stoppedCan my cancer be cured this way ?. The answer to both your questions is that it is highly likely this new 4C strategy will indeed cure your cancer. At this point I think it is by far your best, and quite possibly your only chance.

To know for sure, we will have to take tiny samples of the tumor in your kidney and one or two metastases and send them to a lab to determine which of the genes in your specific cancer are turned on. Those tiny samples will be taken with a biopsy needle. We need just a bit, but it has to come from the specific cancer in your body. Most of your genes, of course, are ones that are necessary for you to live normally. In the cancer, however, you have a number of genes wildly generating their RNA transcripts – generally including multiple oncofetal transcripts which your normal cells do not require, but which are essential for the viability of your cancer. Once we identify those, we can very specifically shut them off with a custom cocktail of transcript-blocking Morpholinos selected specifically for your cancer. That custom cocktail has a very high probability of curing your cancer without harming you.”

Amanda’s mother had tears gathering in her eyes. She wiped them away. “That seems like a miracle. Is that really a possibility, a chance to save Amanda ?

Dr. DeVita furrowed his bushy brows and scrutinized Amanda’s mother before he answered. ” We’ll have to try. Are you willing to go to Oregon ?

* * *

Their taxi driver, a talkative man, smiled as he looked at Amanda and her mother in the rearview mirror. “So you have an appointment at the Institute this morning? Most of my riders are going to or coming from the Institute, and most are from other states or other countries – which has been a boon to Oregon’s economy. A lot of the people coming on Monday morning, like you folks today, go home on Wednesday. That’s the way they schedule ‘em; Monday-Wednesday, Tuesday-Thursday, Wednesday-Friday. A lot of folks go through the Institute. They’ve added extra flights for all the patients. I’m Vince. This is my cell phone number. Give me a call when you need another ride.”

Amanda hoped this trip to Oregon would be a success. She’d been sick twice on the airplane during the flight out and she felt like throwing up in Vince’s cab, maybe from the cancer and maybe from nerves. She dreamed about being well and playing some ball with Mikey. It had been so long she couldn’t even remember feeling good.

A few minutes later Vince turned the cab left through a gate flanked by stacks of black volcanic boulders on each side and then onto a beautiful four-lane parkway lined with trees and grass. The Oregon Institute of Personalized Therapies, a five story earthquake-resistant concrete and glass building, dominated the early morning skyline at the end of the parkway. Four smaller buildings occupied a forest-like park next to the main building. All the buildings displayed the Institute’s emblem of an eagle on wide-spread wings soaring over mountains. A circle drive in front of the main entrance enclosed a small park with a green lawn encircling another pile of huge rocks. A waterfall tumbled its way from the top boulder, over a series of other stones, to a pool at the bottom. A rabbit nibbling the grass next to the pool ignored the cars.

Vince brought the cab to a stop under a canopy shading the entrance to the building. “This is the Institute. It’s quite a place. Almost everyone that comes gets cured – even when they have very advanced disease. I hope you have the same success.”

By the time Amanda’s mother paid Vince, another man in a crisp green and gray uniform met them. “I’m Willard. You have an appointment this morning I assume ?

When Amanda nodded her head, Willard handed both women his card. “I’ll be your usher today. What is your name, please?” He flipped through several pages of names on his clipboard before he found Amanda’s name.

“I see you’re scheduled for the cancer orientation in auditorium A. We have ten thousand patients from the US and around the world coming through the Institute each week. There’s ample chance to get confused so I’ll lead you to the auditorium. My card has my personal phone number. Call me anytime if you have a problem.”

“Ten thousand cancer patients each week !” Amanda exclaimed, wide eyed.

Amanda and her mother followed Willard into the auditorium and down the tiered steps until he showed them their assigned row. He then handed them each a stiff green card. “These have your seat numbers, your names and Amanda’s case number. Please present these cards to anyone helping you with your treatment.”

 

YOUR PERSONAL CURE: Promptly at nine o’clock the lights in the auditorium dimmed and a serious young woman strode out onto the stage. “I’m Dr. Cindy Lyons. Welcome to the Oregon Institute of Personalized Therapies. Let’s be honest. Most of you are severely ill, probably dying, because conventional medicine could not cure you. However, even if your cancer is at an advanced stage it is very likely your personalized therapy which we will provide to you can save you from your cancer.

First, I want to explain why we can cure your cancer when conventional medicine could not. Then I will explain why you had to come to Oregon for your cure.”

“We believe that by far the best way, and quite possibly the only way, to reliably cure your specific cancer, and to do so without harming you, is to treat you with a custom cocktail explicitly designed to safely and completely eradicate your particular cancer. Your custom cocktail contains multiple drugs of advanced design, where each drug is precisely targeted against a different RNA transcript which is absent from your normal cells, but which has been found from a biopsy of your cancer to be present in and essential for the viability of your particular cancer cells. Use of a cocktail of such drugs virtually assures complete eradication of your cancer – without harm to you.”

 

THE REGULATORY PROBLEM: She looked around her audience before going on. “Now I need to inform you that the advanced life-saving therapy you are about to receive from this Institute has not received a conventional regulatory approval from the US Food and Drug Admin. ( FDA ) based on their standard phase 1, 2, and 3 clinical trials program. This is because until very recently the FDA was not prepared to regulate personalized therapies (such as the custom cocktails you are to receive today) in a timely, affordable, and practical manner. Even now, your custom cocktail is approved only by virtue of the FDA’s new unconventional regulatory program explicitly designed for personalized therapies. This demonstration program you are participating in clearly provides a scientifically sound assurance of safety and efficacy. But unlike the FDA’s conventional regulatory programs, the FDA’s new streamlined regulatory program for personalized therapies, now being demonstrated by our Institute only at this single site in Oregon, provides rigorous regulatory approvals in a manner which is timely (days, not decades), affordable (hundreds of dollars, not hundreds of millions of dollars), and practical (3 pages, not thousands of pages of paperwork).”                        

“To put this in perspective, the FDA is mandated by the US Congress to assure that drugs in interstate commerce are adequately safe and effective – based on sound scientific evidence. To meet that legal mandate, over the years the FDA has adopted a huge and constantly growing body of rules and regulations which define in intricate and exhaustive detail how any new drug destined for interstate commerce must be produced, tested, labeled, shipped, marketed, and used. When averaged over both successful and unsuccessful drug candidates, and when both direct and indirect costs are factored in, on average these rules and regulations impose huge regulatory burdens of longer than a decade of delay and costs of hundreds of millions of dollars before the FDA finally gives marketing approval for the average successful new drug.”            

For blockbuster drugs to be used by millions of patients, these exorbitant regulatory burdens may be tolerable – even though they do greatly increase the cost of new drugs.

However, in the case of a personalized therapy specifically produced for a single patient, most of the regulatory burden necessarily falls on that single patient, or on the entity who must pay for that therapy. Not surprisingly, most patients can’t pay( or have paid on their behalf ) the many millions of dollars for approval of a single drug to save their life. Nor can they wait a decade or more for that drug to be approved, by which time all or nearly all such patients would be long dead from their disease. Still further, in regard to demonstrating efficacy, many personalized therapies, including this Institute’s custom cocktails you will receive today, provide high efficacy only against the specific patient’s cancer for which that therapy was designed and produced.”

“Thus, until very recently the FDA’s regulatory requirements had completely stymied development of personalized therapies in the US by requiring far too long and by costing far too much for obtaining regulatory approvals. While development and production costs for personalized therapies can be substantial (weeks and thousands of dollars), it was the regulatory burdens (years of delay and millions of dollars for testing each patient’s therapy) which till now made personalized therapies essentially impossible in the US.

“To remedy this serious deficiency, our Institute’s new demonstration program, authorized by the FDA and assisted by the US National Cancer Institute, is serving to test a new streamlined regulatory process for personalized therapies which is designed to assure the therapies’ safety and efficacy, while now also providing timely, affordable, and practical regulatory approvals.”

To reiterate, like the FDA’s conventional regulations for new drug approvals, the new streamlined regulations for personalized therapies, now being demonstrated at our Institute, require sound scientific evidence for efficacy, and a scientifically sound means for assuring adequate safety. But these streamlined regulations differ sharply from the FDA’s previous rules and regulations by providing timely (days, not decades), affordable (hundreds of dollars, not hundreds of millions of dollars), and practical (3 pages, not thousands of pages of paperwork) regulatory approval for each personalized therapy. Satisfying these new streamlined requirements enabled prompt and affordable approval of the custom cocktail you will receive today for curing your specific cancer.”

“In just the last couple of years this new streamlined regulatory program has greatly accelerated development and use of a host of new personalized therapies. It should be obvious that patients stand to benefit if personalized therapies are allowed to develop and mature in order to fulfill their great promise of safe, effective, and affordable therapies for intractable diseases that conventional drugs have been unable to reliably cure, as well as therapies for rare diseases and conditions for which standard drug regulatory approaches are impractical, or wildly unaffordable.”

Dr. Lyons continued: “Equally important, our new regulatory demonstration project for personalized therapies is serving as a valuable test bed for devising and demonstrating innovative strategies for assuring each drug’s statutory requirements for safety and efficacy – while satisfying those requirements in a manner that is far faster, far cheaper, and far more practical than was possible under the FDA’s conventional rules requiring 3 phases of lengthy and hugely expensive clinical trials.”

“For the above reasons: 1) your custom cocktail has not received a conventional regulatory approval from the FDA based on their standard phase 1, 2, and 3 clinical trials program; and, 2) your custom cocktail can only be produced and made available to you at our single-site demonstration program located here in Oregon.”

“It is noteworthy that here at the Institute we demonstrate daily the feasibility of achieving excellent safety and efficacy for each of our personalized therapies, where those statutory requirements are achieved in days for a few hundred dollars. In fact, our custom cancer therapies virtually always offer patients substantially greater safety and substantially higher efficacy than any of the cancer therapies previously approved by the FDA – where each of those older drugs underwent years to decades of testing at costs of hundreds of millions to billions of dollars.”

 “Our Institute’s fast and affordable regulatory approval process was achieved by focusing from the beginning on how to best achieve high efficacy and safety in the fastest and most cost-effective way. This quadruple focus on safety, efficacy, speed, and cost started with the basic drug design strategy, continued up through each step in the drug production process, and on through the analytical procedures used to confirm identity, purity, and sterility of the final product, and topped off with a laboratory method commonly available since the 1990s (a personalized antidote for each patient) that allows fast deactivation of each of the drugs in the patient’s custom cocktail – in the extremely unlikely event that particular cocktail causes a serious problem.”

               

WHY DEMONSTRATION PROGRAM IN OREGON:
“Oregon is the ideal state to serve as our nation’s test location for personalized therapies – encompassing rapid development, fast and affordable regulation, and unfettered use. This is because of Oregon’s history of innovation in medical care for its citizens. I refer to the Oregon Health Plan, which was designed to provide essential health services at an affordable cost to many thousands of Oregon citizens who previously had no health coverage. That plan was largely devised by Dr. John Kitzhaber in the late 1980s when he was President of the Oregon Senate, and then implemented in the 1990s, largely by Dr. Kitzhaber during his first two terms as Governor of Oregon. Regrettably, that health plan subsequently fell on hard times due to: i) a change in leadership (mandated by Oregon’s term limits on the governorship); ii) a major downturn in Oregon’s economy; and, iii) lack of sustainable funding able to withstand rapidly escalating health care costs.”

“Nonetheless, Oregon’s experience in health care innovation has provided a valuable foundation for Oregon’s new role as a test bed for personalized therapies. It is also noteworthy that the accelerating wave of scientific and medical progress in developing personalized therapies now occurring in Oregon is clearly a result of Oregon’s serving as the test site for such research and development – research and development which had long been stymied by the FDA’s previous slow and expensive rules and regulations. Not surprisingly, this impressive wave of progress, beginning in 2018-2019, has saved hundreds of thousands of lives, provided real hope to many terminally ill patients, reduced health care costs worldwide, and is providing a major boost to Oregon’s economy and tax base.”

“And now our Institute’s custom cocktail technology, which matured in this sheltered Oregon demonstration program, is well on its way to converting cancer

from a devastating and often fatal disease that cost society more than any other disease

to a disease that can be quickly and reliably cured at moderate cost – with no harm to the patient.”

“In regard to costs, the Institute’s custom cocktail, which almost always cures the cancer – without harming the patient, costs $ 25,000 to $ 50,000 – depending on how many Morpholinos in the cocktail. This is much less than the $ 60,000 to $ 100,000 typically required for treatment with conventional FDA-approved cancer treatments that generally devastate the patient, and more than 30% of the time fail to cure the cancer.

“And because cancer is the world’s costliest disease in terms of lost productivity, loss of life, and costs of treatment, we estimate that within a few years our custom cocktail strategy will reduce cancer’s cost to society by 80% to 90%, providing major savings for financially stressed healthcare systems in the US and around the world. These savings to society come from preventing loss of life, maintaining productivity, substantially reducing costs of treatment, and avoiding complications from treatment.”

And for the patients whose lives are saved – the benefits are priceless.

 

MORPHOLINOS: “Oregon also enjoys another major advantage as a test location for personalized therapies. Specifically, the best technology for a wide range of safe, effective, and affordable personalized therapies (Morpholinos [3]) was developed and matured here in Oregon [5] – helped along in the late 1980s by a half-million-dollar equity investment from Oregon’s economic development program funded by its

then-new lottery. That precision-targeted transcript-blocking technology comprises the components of the custom cocktails which will be used later today to treat each of your specific cancers. Since Morpholinos are central to the custom cocktails you will be treated with later today, I will give you a brief history of their conception and development [5], and their broad use in scientific research around the world since the year 2000 [6], as well as describe a 2016/2017 advance in delivery technology which finally opened the floodgates for a broad range of challenging therapeutic uses.”

“Probably the first proposal for blocking specific RNA transcripts for therapeutic purposes was in 1969 [6], but this idea apparently also occurred independently

to multiple other individuals during the 1970s [5]. In Oregon in 1980 Dr. Summerton founded the first company, ANTIVIRALS Inc. (now named Sarepta), focused on developing agents for selectively blocking RNA transcripts. By the mid-1980s this therapeutic strategy was being intensively pursued by a large number of research groups at universities, research institutes, and pharmaceutical companies. Between 1985 and 1989 development of the Morpholino structural type was carried out by Dr. Summerton and co-workers at ANTIVIRALS Inc. By the 1990s the complex technical challenges required for therapeutic success of transcript blockers (commonly called antisense oligos because they bind to the sense RNA transcripts) had become clear, and multiple antisense structural types had been developed for use as targeted research reagents and as targeted therapeutics.”

“In regard to use as research reagents for blocking specific RNA transcripts or altering the splicing of pre-messenger RNAs, many in the scientific community were keen to use antisense oligos for the most demanding of applications, that being use in the field of developmental biology (embryology) for studying the intricate cascades of gene activations and deactivations which are precisely choreographed with respect to both time and position in rapidly maturing embryos. By 1999 nearly all of the available antisense structural types had been assessed as possible tools for studying that extremely complex biological system – but the antisense structural types readily available in 1999 typically just killed the embryos due to inadequate specificity for their targeted transcripts, and due to multiple serious off-target effects. Because of these flaws, even natural antisense structural types, discovered in the late 1990s (siRNA, shRNA and microRNA), gave inadequate results in that most demanding of applications.”

“Then in the year 2000 Dr. Janet Heasman (who studied frog embryos) and Dr. Steve Ekker (who studied zebrafish embryos) discovered that Morpholinos (which had just become commercially available from GENE TOOLS, LLC) gave excellent results in blocking and in modifying splicing of RNA transcripts. Morpholinos’ reliable and predictable activity, even in highly complex developing embryos, was because of their unmatched combination of exquisite sequence specificity, high efficacy, predictable targeting, complete resistance to degradation in biological systems, and a general freedom from off-target effects [4]. Because of Morpholinos’ unmatched combination of superior properties, within a matter of months Morpholinos became the research tools of choice for developmental biologists, and within a few years Morpholinos had revolutionized the entire developmental biology field, allowing scientists to do in days for a few hundred dollars what had previously taken years and tens of thousands of dollars – when it could be done at all [8, 9, 10]. Use of Morpholinos in a variety of model organisms since the year 2000 has led to over 5,000 scientific publications wherein Morpholinos were used as key tools for studying developing embryos [7].”

Researchers in developmental biology have long used only Morpholinos for studies in developing embryos – because nothing else gives reliable results. But until 2016 most cancer researchers wishing to block specific transcripts in cancer cells had routinely used the cheaper siRNAs (and their precursor shRNAs) in attempts to study cancer-related transcripts in cancer cells and in tumor-bearing animals. However, using the cheaper siRNAs was a false economy because siRNAs generally give ambiguous results due to poor stability in biological systems, poor sequence specificity, low targeting predictability, and they are plagued by multiple off-target effects [4].”    

“Therefore, for reliable identification of cancer-essential transcripts Morpholinos are a far better choice because they have been specially engineered (with a novel non-ionic backbone) to provide complete stability in biological systems, exquisite sequence specificity, high targeting predictability, and a general lack of off-target effects [4].”

 

THE DELIVERY CHALLENGE:Because Morpholinos can readily be structured to precisely target virtually any RNA transcript essential to any of a host of different diseases, from their beginning the central motivation in developing Morpholinos was to use them for therapeutic applications in humans [6]. However, by 1993 a number of research groups had come to realize that in almost all cases it is exceedingly difficult to safely and efficiently deliver any large high-information-content antisense drugs, including Morpholinos, into the proper sub-cellular compartment in animals (including humans).”

“By 2004 a means for delivering Morpholinos into cultured cells had been developed which was safe and efficient [11]. And by 2008 several delivery systems had been developed which provided delivery into animals (mice, rats, dogs), but those in vivo delivery technologies [12] were inefficient and moderately toxic – so much so that those delivery technologies were judged unsuitable for delivery of Morpholino therapeutics into humans. Thus, the lack of a safe and efficient delivery technology suitable for use in humans had long prevented most therapeutic applications of Morpholinos.”

“One notable exception has been the successful use of Morpholinos for treatment of muscular dystrophy in mice, dogs, and humans. One such Morpholino drug, named “eteplirsen”, has been shown to be exceptionally safe in humans. By 2015 that drug had progressed through FDA-required clinical trial phases 1, 2 and 3 (requiring more than a decade and costing hundreds of millions of dollars), and was finally approved by the FDA late in 2016. However, muscular dystrophy is a special case because the underlying molecular defect in that disease causes the patient’s muscle cells to self-permeabilize – allowing small amounts of Morpholinos into muscle cells of the patient without need for a delivery system – although such entry is quite inefficient and, at the dose used, Morpholinos give only minimal efficacy in muscular dystrophy patients. Once the Morpholinos gain entry into the muscle cells of the patient, they act, as designed, in the cell nucleus to correct the splicing error in the mutated transcript which underlies that devastating disease.”

“Efforts to develop a truly safe and efficient in vivo delivery system for Morpholinos began at ANTIVIRALS Inc. in 1993, and continued as a joint effort by the spinoff companies: GENE TOOLS, LLC & Onco-Tools, LLC. Late in 2015 a new and quite novel multi-component delivery system was finally devised. By 2016/2017 a new delivery system had been synthesized and tested, first in cultured cells and then in living animals. Test results indicated that the daunting challenges of achieving safe and efficient in vivo delivery of Morpholinos was finally met by a new multi-component in vivo delivery system.”

 “That long-awaited advance in delivery technology finally opened the floodgates for in vivo use of Morpholino therapeutics for precisely targeting RNA transcripts which play key roles in a host of different diseases – including cancers. And it was that crucial 2015-2016-2017 breakthrough in the delivery technology, in combination with recent advances in RNA sequencing, informatics, xenografting human cancers into immune-compromised mice, and the FDA’s new streamlined regulatory rules, which made practical and affordable the custom cocktail which each of you will receive today for curing your specific cancer.”

Dr. Lyons concluded her presentation with a brief summation:

First, the custom cocktail you will receive today has not been tested in conventional 3-phase clinical trials, but the FDA is closely monitoring and independently confirming patient results from our FDA-authorized and NCI-assisted program to demonstrate a streamlined regulatory program designed expressly for personalized therapies.

Second, your custom cocktail for your specific cancer has already been experimentally confirmed to be effective for killing the cells of your specific cancer. This was achieved by taking a portion of the biopsies of your cancer and growing and treating your cultured cancer cells to experimentally confirm your cocktail kills your specific cancer.

Third, the transcript-blocking drugs which make up your custom cocktail provide a superior combination of properties unmatched by any other transcript-blocking technologies.

Fourth, in the very unlikely event that your custom cocktail causes a serious problem, a personalized antidote will be quickly assembled and injected to reverse that problem.”

Finally, your doctor has already provided our Institute and the FDA with a brief summary describing: your type of cancer; its treatment history; and its stage just prior to your treatment today here at the Institute. Now we are also requesting that same doctor also describe the status of your cancer two months afteryour treatment here at the Institute, plus an update on your health 1, 3, and 5 years after your treatment here at the Institute. Over time, this information allows the FDA to make a rigorous ongoing comparison of the safety and efficacy of our new custom cocktail treatment versus the conventional FDA-approved cancer therapies widely used elsewhere in the USA.”

At the end of Dr. Lyons’ presentation, everyone in the audience inserted their green ID cards into a turnstile as they left the auditorium, which returned a card with a room number before it let the person pass. Amanda was assigned to Room 3-D-57.

A young man with a friendly smile met them on the third floor and led then to hallway D having a long row of rooms on both sides of the hallway. He escorted them to Room 57 and introduced them to Edith Hadley, a pleasant-looking nurse dressed in a green and gray uniform with the Oregon Institute’s soaring eagle embroidered on the front.

A curtain separated the table and chairs in the first part of the room from an adjoining space equipped with a small bed covered with a white sheet, an easy chair, and a tall chrome pole holding an assortment of plastic bags and multiple tubes. Butterflies filled Amanda’s stomach at the sight of the gleaming medical equipment and the narrow bed.

Nurse Hadley examined their green ID cards and compared their names and Amanda’s patient number to some papers on her clipboard. “Please sit down. Do you have any questions about what we are doing today?”

 

CONFIRMING EFFICACY & ASSURING SAFETY:
Amanda’s mother squirmed in her chair, with her gaze on Nurse Hadley, and finally began. “Amanda and I understand that by analyzing a biopsy sample of Amanda’s cancer your experts were able to identify just which cancer-essential transcripts are causing Amanda’s
cancer. And with that RNA transcript information your experts assembled a custom cocktail of five drugs targeted against five of those transcripts causing Amanda’s cancer. However, as we understand it, there are billions of possible individual cocktail combinations which could be assembled from your Institutes’ arsenal of transcript-blocking Morpholinos. Thus, the particular cocktail which will be used to treat Amanda has probably never been made before, and has probably never been tested in any lab animal or human.”

“How then do we know if her cocktail will work ? And that it will be safe ? What if they picked the wrong transcripts, or the treatment kills the wrong cells ? Won’t that make my baby sick or kill her ? What about that ?

Nurse Hadley replied: “In regard to evidence that Amanda’s custom cocktail will work against her particular cancer, this has been explicitly tested in what we call our “evidence-for-efficacy” test. When her doctor sent her needle biopsy samples, frozen in dry ice, one portion of the cancer cells in those samples was cultured and the cells distributed into multiple wells in a 96-well cell culture plate. A few days ago, before we assembled the five transcript-blocking Morpholinos to form Amanda’s custom cocktail, we carefully tested on Amanda’s cultured cancer cells the effect of each of those five individual Morpholinos, plus the effect of the combination of those five Morpholinos. Only after we had confirmed that each of these individual Morpholinos, and the combination, effectively killed Amanda’s cultured cancer cells, did we assemble the much larger quantities of these same five Morpholinos to produce the custom cocktail which we will treat her with today. Thus, even before treating Amanda with her special custom cocktail, we have obtained compelling experimental evidence that her particular cocktail effectively destroys her particular cancer cells.

Thus, when those five transcript-blocking Morpholinos are injected into Amanda’s vein, those Morpholinos will hunt down and block five of the essential transcripts which were found to be running wild and causing her cancer, where each such transcript is essential for one of the key cancer-causing hallmark pathways which are only present in her cancer cells, and which are essential for the continued viability of her cancer. When those multiple transcript species are blocked it will turn off those pathways essential for the viability of the cancer, and thereby kill the cancer – without harming Amanda.”

Nurse Hadley continued. “In regard to safety, Amanda’s cocktail is inherently far safer than conventional cancer therapies, and much safer than most doctors might imagine – for two reasons. First, each of the component transcript-blocking Morpholinos has been individually tested for safety in 50 healthy persons, and each transcript-blocker was found to be free from significant adverse effects in those healthy persons – as was expected because the oncofetal transcripts targeted by those Morpholinos are simply not present in normal adult cells. Second, in the highly unlikely event that Amanda has a bad reaction from her custom cocktail, we have ready the exact components for her personalized antidote” capable of rendering inert Amanda’s already-delivered custom cocktail. To provide this exceptional extra level of safety, when our experts assembled the specific cocktail of transcript-blockers for Amanda, they also prepared the exact complements capable of quickly hunting down and rendering inert each of those transcript-blockers of Amanda’s custom cocktail. Thus, in the very unlikely event Amanda has an adverse reaction to her custom cocktail, her personalized antidote will be quickly assembled and injected into Amanda to halt that adverse reaction.”

To reiterate:

 1. EFFICACY:
Each component in Amanda’s cocktail has already been confirmed to kill the cancer cells from Amanda’s cancer.

 2.   SAFETY:
Each component in Amanda’s cocktail has been shown to be non-toxic in 50 normal adults.

3.   EXTRA SAFETY:
In the very unlikely event of an adverse reaction due to Amanda’s cocktail, her “personalized antidote” will be quickly mixed and injected to render inert Amanda’s already-delivered cocktail – thereby halting that adverse reaction.” 

“After Amanda’s single treatment, the Morpholinos of her cocktail will enter the cytosol-nuclear compartment of cells of her body thanks to a new multi-component delivery system. Within her cancer cells the Morpholinos will selectively block or modify their targeted cancer-essential transcripts – causing those cancer cells to die. The dead cancer cells will then be disposed of by her body over the course of the next few days. Because Morpholinos have a special molecular structure which is not degraded within cells (not even within lysosomes), any surviving cancer cells will remain under attack by the cocktail of Morpholinos for an extended period of time (at least weeks), which serves to assure the complete destruction of all cancer cells exposed to Morpholinos from the single initial injection. For cancer cells within the central nervous system, several special delivery strategies are used to assure attack even in those cancer cells shielded by the blood-brain barrier.”

 “As the cancer cells die over the next few days, Amanda will first notice that her pain decreases and then it will disappear. Her urine will no longer contain blood and her vision will return to normal. In two months the tumors all around her body will be gone. She will be cured.”

 “Then, Amanda,” her mother said, “if you’re ready, let’s do this. It seems safe and we really don’t have any reasonable alternatives.”

 Amanda nodded in agreement. “I want to get my life back.”

 Nurse Hadley handed a clipboard to Amanda’s mother. “If you agree, and have no more questions, please sign each of these three pages.” While Amanda’s mother reviewed and signed the papers, Nurse Hadley led Amanda into the adjoining area with the medical equipment and stepped on a pedal to bring the top of the bed into a sitting position. “If you’re ready, please get in a comfortable position on the bed.”

Within a minute Nurse Hadley had cleaned Amanda’s left forearm with alcohol and put a rubber tourniquet around her arm above the elbow. She tapped a bulging vein with her gloved hand. “That’s a good one. You’ll feel a little prick when I insert the needle, and then I’ll hook up the intravenous tube.”

 Amanda grimaced but forced herself to watch the needle enter the vein in her arm, almost without feeling anything. Within seconds the nurse had the needle connected to one of the clear plastic tubes dangling from the chrome pole. Amanda watched as a clear liquid flowed through the line and into her arm.

Nurse Hadley took the vial with Amanda’s custom cocktail and double checked the name and patient number, and then asked “Are you ready to eradicate your cancer?”

 Amanda nodded and Nurse Hadley inserted the stopper end of the tube into a connector in the plastic tubing. “This is your treatment.” Nurse Hadley pushed a plunger in the vial and its life-saving contents flowed into Amanda’s arm.

Amanda closed her eyes and laid back on the bed as she imagined the army of invisible life-saving Morpholinos pouring into all the cells of her body. She smiled. Minutes later Nurse Hadley removed the needle in Amanda’s arm. “You’re done. Research in animals indicates that your cancer-causing transcripts will be disabled within a few hours, all the cancer cells will die within the next few days, and your body will heal.” She patted Amanda’s arm and grinned. “Congratulations, Amanda.”

Amanda’s mother had risen to her feet. “Is that all there is to it ? Are we done ?

“That’s the treatment. We want Amanda to stay here for an hour to be sure she is fine. We will also check her Tuesday and Wednesday. You can go home Wednesday.”

Amanda steped down from the bed. “When will I know it worked?That I am cured ?

“You are scheduled for a follow-up scan in two months. Your cancer should be gone by then. You’re a lovely young girl with all of your life ahead of you. Good luck.” Nurse Hadley gave Amanda a parting hug.

* * *

Two months later Vince met Amanda and her mother at the airport for the drive to the Institute. Amanda already knew that her cancer had been cured. She felt good, really good, and she could again play ball with Mikey. Her pain, the blood in her urine, and the problems with her vision had all disappeared within six weeks of her initial visit to the Institute. Her nightmare of cancer was over.

But in spite of all of her own good news, and the happiness and relief that came from being cured, she was also experiencing an overpowering feeling of sorrow.                           

 

AN UNNECESSARY TRAGEDY: A month earlier Amanda and her best friend Sylvia had been selected for the 2020 state-wide math tournament. Shortly after that, Sylvia started having problems eating, throwing up. By an awful stroke of fate, Sylvia had pancreatic cancer that had already begun to metastasize. Sylvia’s mother and father adamantly refused to let her be treated with any therapy that had not been approved through the FDA’s conventional three lengthy and expensive clinical trial phases. Sylvia’s parents believed they were protecting her from quack medicines.

They’d said: “Amanda was just lucky”, and they insisted “Sylvia can have surgery to remove the cancer, then conventional FDA-approved chemotherapy drugs can be used to destroy any small cancers that may have invaded other organs. That’s how cancers should be treated – with conventional therapies exhaustively assessed for safety and efficacy in three clinical trial phases with thousands of test subjects over many years, and then conventionally approved by the FDA.”

Amanda and Sylvia had checked the internet for the chances that Sylvia could be cured. She’d lose all of her lovely black hair, endure six months of misery, and still have little hope because conventional cancer treatments were almost always unsuccessful for late-stage pancreatic cancers which had metastasized. Sylvia wouldn’t join her in the math contest, and probably wouldn’t grow up.

Amanda grieved for her best friend.

 

POST SCRIPT

 

TRAGEDY AVERTED: A few months after Sylvia’s diagnosis of pancreatic cancer, her mother and father came face to face with the harsh reality of conventional FDA-approved cancer treatments, and particularly the ravages of chemotherapy. This led them to reconsider their adamant refusal to let Sylvia be treated with the new precision-targeted custom cocktail treatment available only in the FDA-authorized demonstration program in Oregon.

While re-assessing their initial refusal, Sylvia’s parents had found on the internet glowing personal testimonials from cancer patients claiming almost-miraculous recoveries after treatment in Oregon with the precision-targeted custom cocktails – even from patients with a wide variety of late-stage metastatic cancers.

But on digging deeper, they also found on the internet similar almost-miraculous claims for treatments with homeopathic medicines, fanciful cancer-curing devices, natural products that had failed all controlled laboratory tests – but were being pitched to desperate patients simply because the products were from natural sources, as well as many other modern versions of the proverbial “snake oil”.

However, they also found a rapidly-increasing number of scientific reports from cancer research labs describing compelling evidence that commercially-available precision-targeted Morpholinos specifically and decisively blocked the function of their targeted cancer-specific RNA transcripts – both in cultured human cancer cells, and in human tumors implanted in immuno-compromised mice (called mouse xenograft models). These peer-reviewed research reports were particularly reassuring because they were simply recapitulating the rapid adoption of Morpholinos for studying the intricacies of embryo development – which between the years 2000 and 2016 led to over 5,000 peer-reviewed scientific publications, and revolutionized the field of developmental biology [7, 8, 9, 10].

However, the information that finally persuaded Sylvia’s parents to take her to Oregon for treatment was documentation posted on the internet by the FDA. That information, being regularly collected by the FDA directly from patients’ oncologists, described and tabulated actual patient post-treatment responses from the “custom cocktail treatments” in Oregon. For comparison, the FDA also provided corresponding post-treatment responses from similar patients with similar cancers – but who were instead treated with conventional FDA-approved cancer therapies.

While there was only a little over a year of such comparison data, and early results from only a limited number of custom-cocktail-treated patients, it was abundantly clear that patient response trends between the “custom cocktail” treated patients and all the conventionally-treated patients were strikingly different (as different as live patients versus dead patients). This argued strongly that the glowing personal testimonials from patients claiming almost-miraculous recoveries with the new treatment were indeed for real, and not just internet hype.

This information from the FDA, plus her friend Amanda’s recent experience with this custom cocktail treatment, finally persuaded Sylvia’s parents to take her to Oregon for treatment. Not surprisingly, Sylvia made a rapid and complete recovery.

Thus, Sylvia’s case provided still further “preliminary” evidence suggesting that precisely targeting multiple cancer-essential RNA transcripts, which had been determined to be present in a given patient’s cancer, can apparently achieve rapid and complete annihilation of that cancer without harm to the patient.

 

REFERENCES

  1. V. DeVita and E. DeVita-Raeburn (2015). The Death of Cancer. Sarah Crichton Books, New York
  2. [A] J. Summerton (2016). Custom Cocktail for Curing any Cancer: A strategy for destroying any cancer without harming the patient. Journal of Drug Discovery, Development, and Delivery, 3(1): id 1020.
  3. [B] J. Summerton (2003). Custom cancer therapies: safe and effective treatments for most or all cancers. Annals of New York Academy of Science 1002: 189 – 196.
  4. https://en.wikipedia.org/wiki/Morpholino 
  5. J. Summerton (2007). Morpholino, siRNA, and S-DNA Compared: Impact of structure and mechanism of action on off-target effects and sequence specificity.
  6. J. Summerton (2016). History and Properties of Morpholino Antisense Oligos. Journal of Drug Discovery, Development, and Delivery, 3(1): id 1019.
  7. J. Summerton (2017). Chapter 1: Invention and early history of Morpholinos: From pipe dream to practical products. In: Morpholino Oligomers: Methods and ProtocolsEd. Moulton & Moulton.
  8. pubs.gene-tools.com
  9. J. Heasman (2002). Morpholino oligos: Making sense of antisense ? Developmental Biology, 243: 209 – 214.
  10. S. Ekker (2000). Morphants: A new systematic vertebrate functional genomics approach. Yeast, 17: 302 – 306.   
  11. SPECIAL ISSUE (2001). Morpholino Gene Knockdowns – all 27 research reports in the July issue of the journal: Genesis, 30: 89 – 200.
  12. J. Summerton (2005). Endo-Porter: A novel reagent for safe and effective delivery of substances into cells. Ann. N.Y. Acad. Sci., 1058: 62 – 75.
  13. Y. Li and P. Morcos (2008). Design and Synthesis of Dendritic Molecular Transporter that Achieves Efficient in vivo Delivery of Morpholino Antisense Oligos. Bioconjugate Chem., 19: 1464 – 1470. Current Topics in Med. Chem., 7: 651 – 660.