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Revision as of 14:22, 4 November 2016

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.

Killing cancer 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.

Focus on 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 combination 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) Use combination of a low dose of Opdivo and Yervoy (Checkpoint inhibitors) 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 CDMA-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.

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.