Immune Strategy
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Purpose
I'm Marc Perkel. I have non-small cell lung cancer (NSCLC) with RET mutation. Diagnosed stage 4 on august 1 2016. I'm working on a strategy to see if I can beat this. I know the odds are extremely against me but even if this is a hopeless battle I still intend to put up a fight well fought. All my life I've been know as a "brain" and I am self taught in a variety of fields. It is not unusual for me to figure out things that no one has figured out before. And with my very existence on the line I'm highly motivated to be successful.
It is my hope to inspire thought about this and for experts in the field to be inspired by these ideas in the hope of developing a cure. I'm no cancer expert, but this has to be at least a very good guess.
The Big Picture
This article is about looking at the cure for cancer from a big picture perspective. Think of all the different ways cancer is treated as if you were putting together a picture puzzle. Are some point you zoom out and look at all the pieces, not as separate treatments, but as part of a big picture that tells a complete story about the nature of cancer and ties together these treatments into a singular vision of the whole system.
In this article I'm going to talk about a new paradigm and a new way of thinking about the cancer cure problem. The new paradigm includes:
1) Combinations, Sequences, and Plans - Going from single treatments to combinations to sequences of combinations. It's a symphony, not a series of solos.
2) School not War - Educating the immune system is the goal. Directly killing the cancer is not.
3) Understanding the Mechanisms - what causes old people to get cancer? The role of the immune system in preventing cancer. Curing aging as a key to cancer treatment and prevention.
4) A new way of thinking about the problem - Projecting what the cure will look like when we cure it and working backwards from there to where we are now.
A different way to look at the battle against cancer
We are waging a battle against cancer where the focus is on killing the cancer. Maybe there is a better solution to the problem. Perhaps the focus should be on training the immune system to kill the cancer rather than trying to kill the cancer directly. The body already has its own anti-cancer army. Rather than doing battle with the cancer directly we train our body's natural defenses against cancer to the the job for us.
Killing cancer directly might not be the best goal
The normal way to fight cancer has been to attack the cancer to kill it as hard as possible. When cancer returns you try to kill it again with something else, and then repeat to patient dies of either the cancer of the side effects of the treatment. Although this can buy some time, when it comes to the fatal cancers the cancer always wins in the long run.
Perhaps the idea of killing the cancer directly is a flawed idea. Maybe there's a better way? Maybe if we looked at what a cure for cancer might look like and then think backwards from the solution to the problem we can arrive at something that is more likely to be the cure?
I'm going to do a thought experiment here and I'm going to propose what I think the cure will be when lung cancer is cured, and then work backwards from the cure.
The Cure for Cancer is School - not War
I propose that the cure for stage 4 lung cancer is when the immune system is trained to recognize the cancer and all of it's mutations and kills the cancer and similar cells that are genetically and chemically related to the cancer. So the immune system is smart enough to recognize the cancer and all it's mutations so that the cancer can't evolve out of it.
So what mechanism can do that? The adaptive immune system. So if the above premise is correct - then the goal is to teach the adaptive immune system to recognize the cancer and all its variants and to be able to find and kill it. Therefore we need to forget about deliberately killing the cancer and focus on the training.
Since this is school and not war then perhaps we can take advantage of a new way of thinking. Rather than poison the patient to the verge of death in order to decimate the cancer as much as possible we can use lower dosages and take advantages of a lot more concurrent substances in combination, and sequence treatments in an order that is optimized for adaptive immune system training rather that a war on cancer strategy. The reader is now encouraged to forget the usual paradigms and to think more in low non-toxic dosages with few side effects for the purposes of maximizing training rather than killing.
Why older people get cancer
The number one cause of cancer isn't smoking - it's old age. While there are some specific cancers that are genetic or the result of toxic exposure, most cancer happens to people as they get old. Even among smokers they usually don't get cancer from smoking until they age.
So why does age cause cancer?
Actually - our bodies are making cancer all the time whether we are young or old. But in young people our immune system finds and kills the cancer preventing the mutated cells from getting a start. So cancer isn't something we "get" but something we fail to stop. The key to understanding cancer is understanding evolution.
Think of evolution as trying different things randomly and that 99.9999% of the time the mutation fails and/or the immune system kills it. But eventually a mutation happens where it is a viable organism and somehow avoids detection. So the cells produce a small colony. The continue to mutate and eventually avoid program cell death (apoptosis) recruit a blood supply, and have the infrastructure to produce tumors.
As we get older the genetic switches that differentiate our cells lose integrity causing cells to lose their genetic identity. This isn't as much genetic variations but the switches that differentiate cells so that blood cells are different that skin, liver, or brain cells. As we grow older the switches (histomes, epigenetics) start to fail and genetic integrity is compromised.
If the immune system maintained its strict standards it would kill off all the aging cells, but if it did that we would all die of autoimmune disease at the age of 40. So in order to not go into immune suicide one has to assume that the immune system alters itself to be more lax in what it allows. Because more "normal" cells are less normal the immune system become generally more permissive, and because of this, more cancer manages to sneak through security and eventually evolve into tumors.
The important point here is the relation between the immune system and cancer. That cancer happens all the time and that the immune system is the first line of defense against cancer. And it is therefore logical to harness the immune system as the main resource in the cure for cancer. And that the reason cancer exists is that the immune system failed to stop the cancer, and giving the immune system the ability to fight the cancer is the key to the cure.
Anti aging technology and Cancer
There is a lot of serious work happening in the anti-aging world. Although age is a function of time, aging is a function of biology. Our bodies are not like owning an old car that is slowly wearing out and rusting away. Our cells are being killed off and reborn on a regular basis. So you're literally not the same person you were 20 years ago. All your cells have died off and been replaced with new cells.
[Dr. David Sinclair] has been working for the last 20 years on the assumption that aging is a curable condition and that a person can be restored to a younger state on a cellular level. His work is quite promising and his latest substances are now in human trials. He's the guy who discovered Resveritol in red wine as a life extension substance. Since then he's discovered more powerful substances and some of these are now sold on Amazon as nutritional supplements. In particular, the combination of N (R) Niagen Nicotinamide Riboside and Pterostilbene is a powerful combination. Newer substances are not yet available to the public.
The hope and promise of his work is focused on the [Sirtuin] pathways and refers to 7 enzymes that clip off genetic crud off the histone receptors which restores genetic integrity. Thus the individual doesn't experience genetic aging and has the immunity of a young person to the diseases of old age including cancer, diabetes, dementia, Alzheimer, and heart attacks. The hope is that this will increase life span from 80 years to 120 years and that these extra years are healthy years.
Although there are a lot of quacks in the anti-aging world, there are some serious substances being discovered as well. And what I notice is that all the same substances that appear in the anti-aging world also appear in the anti-cancer world. And the same mechanisms are references as well. In particular the mTor pathway is prominent in both worlds. And this is no surprise. Since cancer is caused by aging then it is logical that curing aging would tend to prevent cancer. And perhaps it would at least be part of the cure for an existing cancer.
One would assume that at least a healthy younger cellular state would at least be a more hostile environment for the spread of cancer and would extend overall survival numbers in existing cancer. However preventing cancer and curing an existing cancer isn't the same thing.
The Adaptive Immune System
Training the immune system appears to be the holy grail of cancer cure. Instead of fighting the battle directly by poisoning the patient to the verge of death in the hope of killing the cancer even more, what you do is train the local army that we all have to attack and destroy the enemy. Most of us have a strong enough immune system to easily defeat the cancer, but the problem is that the immune system fails to identify the cancer. Cancer isn't successful by being stronger than the immune system, but rather being invisible to the immune system. The solution is to give the immune system the ability to identify the cancer. So it's about taking the immune system to school.
The immune system has many components, one of which is called the adaptive immune system. It works a lot like my spam filter system that blocks spam emails and passes good emails. It has the ability to learn and identify trillions of chemicals. As you are exposed to viruses, bacteria, and toxins the adaptive immune system learns these and makes the body more resilient to disease. We have been able to prevent disease through vaccination. Vaccination methods include injecting someone with a weakened or dead form of a disease that the patient can defeat, but the adaptive immune system "learns" the substances in the disease so that when exposed to the real thing the immune system immediately recognizes it as the enemy and defeats it.
The important point here is that the immune system has no trouble usually in defeating the enemy, but fails to identify the enemy. And since cancer comes from our own cells cancer is harder to identify, especially as we age. So the trick is to learn to identify the cancer as the enemy and go after it.
Going after Cancers - not Cancer
One mistake I think is common is looking at the cancer as a single target rather than a colony of closely related targets that might have many mutations. What happens is that we target and defeat one cancer just to have a slightly different version of the cancer grow that is resistant to the treatment. And this is why I think conventional treatment fail in cancers which have a higher spectrum of mutations. So they kill one cancer just to be replaced by the next cancer in line.
Using an immunotherapy strategy the idea is to target all the cancers at the same time so that the immune system learns not just one cancer, but all the cancers at once. The immune system learning all the cancers would produce multiple antibodies. And the presence of multiple antibodies would more likely be able to more broadly identify more yet unknown similar cancers creating a broader and smarter immune response.
Thus using multiple kill techniques at the same time, but in lower dosages so as not to create toxic side effects, creates a learning environment that allows the body to create a more effective vaccine against not just a cancer, but all cancers in the body and similar cancers that might occur in the future.
The important point - multiple attacks using multiple methods at lower dosages in order to release training information rather than to directly wipe of the cancers - and then let the army of the adaptive immune system do the dirty work.
Steps in Adaptive Immune System Training
I see the problem a having 3 parts. All 3 parts need to be done in order for the body to generate an anti-cancer vaccine that is finely tuned the the specific cancer(s) that the patient has.
1) The immune system needs to unmask the cancer if the cancer is wearing a disguise and expressing chemicals that send the "friend" signal to the immune system. Examples are PD-L1 and CDMA-4. These friend signals are defeated by "checkpoint inhibitors. The more disguises that can be unmasked simultaneously the more effective the classroom. Rather that quantity the better strategy is variety. A little bit of everything exposes more cancers to be identified and learned.
2) The cancers need to be actively be killed so as to release the "smell" (antigens) into the environment. Dead and dying cells trigger a vaccination effect allowing the adaptive immune system to identify the target as the enemy. Again the key here is to simultaneously kill all the varieties of cancer at the same time so that all forms the the cancer release their smells. That way you don'y end up killing one cancer just to have a slightly different cancer return.
3) The immune system needs to be stimulated and put into a learning more so that it is ready to go for the attack. Things like fever sound the alarm and rally the troupes for battle.
The important point is that all three of these need to happen at the same time. And conventional therapies don't do that. But researchers are discovering that killing cancer with radiation combined with immunotherapy adds to the effectiveness. So there is evidence that supports this hypothesis. But the idea is to transition from a blunt attack to a precision strike and think in terms of training the immune system rather than killing the cancer. And to appreciate timing and sequences that enhance the biological classroom created within the patient's body.
Method for training the Immune System
In order for the immune system to learn cancer you need to:
- 1) Kill / wound enough cancer to allow the "smell" of the cancer to be out there for the adaptive immune system learn from. I'm thinking several things to kill cancer in different ways so that the "smell" (Antigens) can be released using multiple mechanisms with the idea that multiple mechanisms is better than one. But since the idea is to release the smell rather than to kill these multiple mechanisms can be used concurrently in far lower dosages and avoid the toxic side effects you would have in an environment where you are focused on killing.
- a) Targeted kainase inhibitors (Caprelsa, Alectinib) at lower dosages to kill / wound cancer more slowly and reduce side effects. This drug and similar drugs target the RET fusion mutation and will release the smell of cancer cells carrying the RET mutation.
- b) Use mTor inhibitor (Afinitor) combination to make targeted inhibitors more effective in low dosages and go after multiple pathways at the same time.
- c) Anti-aging drug combinations such as N (R) Niagen Nicotinamide Riboside with Pterostilbene which is a metabolic stimulator and also another mTor inhibitor and restores cell integrity by repairing epigenetic damage caused by aging. Sine cancer is primarily caused by old age the reversing old age should be a step towards curing cancer. Pterostilbene induces apoptosis which is another mechanism for spreading the smell of dying cancer into the immune environment. And this combination is not toxic so there is no down side.
- d) Radiation in low dosages - not to try to kill the tumor - but to kill / wound enough to create the smell of dying cancer. There are several studies that combine immunotherapies with radiation where the radiation is used for the purpose of training the adaptive immune system to recognize the cancer.
- e) Hypothermia - heating of the tumor inhibits cancer growth through several mechanisms.
- 1) Apparently rapidly diving cells are more susceptible to be damaged by heat than normal cells contributing to death of all malignant growths regardless of their mutations. This gives the immune system a wider variety of cells to taste.
- 2) Induction of an artificial fever causes the body to think it's under attack by and infection and the immune system goes into a heightened state of readiness as the alarm is sounded and the white blood cells go out to look for an enemy to kill. So in an environment where the cancer smell is being released at the same time the white blood cells are primed for an attack looking for trouble.
- 3) Hypothermia can be induced using low tech means. A thermo gel cooling cap is placed in the freezer and the patient gets in a tub of hot water while the brain is cooled by the cooling hood. Because the thermostat is in the brain the coolness of the brain allows the body to hear up to fever temperatures signaling the attack. This would not likely have any toxic side effects.
- 2) Checkpoint Inhibitors - Use combination of a low dose of Opdivo and Yervoy to unmask the cancer will suppress the "I'm a friend" signal that cancers evolve to cloak itself from the immune system. This PD-L1 and CDLA-4 are eliminated and the immune system can now see the cancer as the enemy and attack it. And again - rather than using dosages that have toxic side effects the idea is to learn the cancer rather than go to war. And to time the lower dosages to unmask the cancer in an environment there cancers are being killed by targeted inhibitors, anti-aging mTor compounds, low dose radiation, and hypothermia.
- 3) Immune System Boosters - Seems logical at the same time to boost the immune system to get the immune system in a very active state for learning. Perhaps something like hypothermia would induce an artificial fever and activate heat shock proteins. Also wondering if getting a flu shot at the same time as check point inhibitors would boost the immune syatem or injections of Coley's Mix Bacterial Vaccine.
Classroom vs. Battlefield
The important point here is that using low dosages from as many as 10 substances at low dosages create a "classroom" rather than a "battlefield". And - this is the important point - if the classroom is successful, the cancer is cured. The immune system has learned the cancer and all variations and mutations of the cancer and the patient's body creates a vaccine against the cancer so that the cancer goes away and stays away.
Since this is a classroom environment rather than a battlefield the idea is to use far lower dosages with little or no side effects. The lower dosages that focus on training rather than killing allow more treatments to be use in combination and to take advantage of synergistic effects by not only combining drugs but complementary mechanisms and to also embrace a strategy that involves sequencing and timing so that different mechanism work together in and orchestrated battle that leads to a permanent victory where the patient wins in the end.
Sequencing is Important
The big picture is the right combinations in the right order. Where we want to be in the end is with an adaptive immune system that knows the cancer and can identify cancer variation so it can kill the mutations as well. The sequence would be:
1) Reverse aging - use of anti-aging compounds not only attack cancer but narrow the genetic profile of normal cells to a smaller genetic range. Thus the immune system becomes less tolerant of the epigenetic variations of old age making a stronger differentiation between cancer and normal cells. Anti-aging substances should be used in normal aging people to prevent cancer and other old age diseases to prevent cancer in the first place.
2) Release the smell - kill some cancer focusing on multiple mechanism to kill a little of all the cancer variations in the body. It would be more accurate to think about the cancers as being multiple kinds of organisms and the idea is to make sure that multiple methods are used to kill a little of everything for the purpose of training the adaptive immune system to all the cancer variants.
3) Unmask the enemy - use checkpoint inhibitors to unmask the cancer allowing the immune system to find the enemy and learn it.
4) Unleash the hounds - Boost the immune response to let the body go into learn and attack mode and wipe out the cancer.
Conclusion
Since current methods don't work it is obvious we need to try something new. What does work in a small number of patients is that immunotherapy is taking a small percentage of incurable cancers all the way to the cure. It is not yet well understood why it works in some people but not in others. I suggest that the lucky ones are the ones where their adaptive immune system has gone to school and has learbed the cancer and its variants and is able to completely eradicate it. I suggest that possibly the above strategy might be the process where the number of immunotherapy patients get to the cure can be increased.
This plan introduces some novel ideas worth exploring. The paradigm shift from battlefield to classroom opens up the possibility of using dozens of drugs simultaneously and lower dosages in order to exploit synergies without toxic side effects. It also focuses on sequencing and timing so that the adaptive immune system is trained in a target rich environment and while the masks are removed at the same time. The sequencing is a much tighter time frame that the current paradigm of first, second, and third line attacks in an unrelated order. The sequencing allows the attack to be orchestrated rather than sequentially lashing out using unrelated attacks.
The proposal here is intellectually elegant and is more like an overall battle plan. It extends the idea of combination therapies that seem to be very much in favor in the oncology world. But instead of just combining substances it combines mechanisms and sequences mechanisms in a logic order. And it follows the current evolution of oncology research. We are going from single drug therapies to combination drug therapies already. We are also seeing immunotherapies achieving complete cures in a small fraction of patients, and we are beginning to understand the mechanisms where aging leads to cancer.
The idea here is to put these isolated features that we currently understand into a big picture there the pieces of the puzzle fit together into "the big picture". We are going from single drugs to 2 combination drugs. What's the next step? 3 drugs, 4 drugs, 10 drugs? But to do that you have to lower dosages and count on synergies. And then there sequencing of mechanisms which seems to be an obvious next step after combinations.
Imagine you are 20 years in the future looking back at the days when everyone died of lung cancer. And now you know what the cure looks like and what you figured out over time. I suggest that when we look back we will have figured out much of what I'm presenting here. So - why wait 20 years when we can do it now? This makes sense and is logically the extrapolation of combining all the stuff we know today.
Disclaimer
I - Marc Perkel - am not an oncologist. I have an unusual ability to figure things out very quickly and come up with big picture solutions to problem I barely understand. I have done this all my life in a wide variety of fields. You can Google my name to see what I'm talking about.
So what that means is that much of the details of the above information is wrong. I'm just beginning to learn and understand the big words that I learned from reading and watching YouTube videos. But in spite of my lack of experience and training I am highly confident that the ideas presented here are likely to be a big step towards a solution to the problem.
I wrote this in part to form an argument to persuade my oncologist to be ready for my request for prescription to actually try this out on myself. Being that I have a fatal diagnosis the way I see it is - what do I have to lose? And when I do lose I want to go down having fought a glorious battle (Think Klingons/Star Trek) with my hands around my enemy's throat.
But my intent is also to inspire a new way of thinking for cancer researchers so that if you are reading this you might say that these ideas are worthy of discussion, exploration, and that you improve upon these ideas and cure these cancers. And it is my hope that you can mentally put aside the idea that some patient with no training can in a 3 month period of time solve problem that thousands of highly educated researchers haven't solved. I do this sort of thing all the time. And the world would be better off if you can keep me alive long enough to figure out how I do this.
Contact Me
I welcome contact especially from oncologists and researchers and would like feedback on these ideas so that this can be acted on and enhanced. I would like to talk on the phone to cancer experts about my ideas and someone who can educate me and answer my very thoughtful questions.
Feel free to contact me @ marc@perkel.com Twitter: @mperkel
