Albert Einstein is said to have defined insanity as “doing the same thing over and over again and expecting different results”. This great scientist went on to say that “Any intelligent fool can make things bigger, more complex and more violent. It takes a touch of genius – and a lot of courage – to move in the opposite direction.”

You may interpret the above quotations anyway you like and for whatever reason or circumstances you like. Let me put them in the perspective of my own work – herbal therapy for cancer. If I have patients coming to me  every day and I prescribe  A, B or C to them and they don’t get well. I must be a real idiot to keep on giving out the same A, B or C to them again and again hoping that one day someone get cured!

To avoid being an idiot, I tell patients to stop taking our herbs if they feel that they are NOT getting any better after two or three weeks. We do not want to mislead you nor waste your precious time. I take this stance because I really believe in what Einstein said.

There is another lesson I learnt from Einstein. To him complex problems may not need complex answers. There can  just be a simple answer to it! But the problem is, many people in this world want to believe that a complex problem must have a “scientific, complicated and complex” answer. That is why we end up with having “experts.”

These so-called experts are highly educated people who talk a language that you and I may not understand. They make things to appear complicated and complex (so that their expertise are always required!)  Let me repeat, any intelligent fool can make things bigger, more complex and more violent. It needs a real touch of humility, courage and a lot of common sense to see things differently. In short, complex problem can just be solved simply! Unfortunately again, to many people simple answers are not impressive – too good to be true!

For the past week,  I spent some time surfing the net in addition to reading a book.  I have shared with you what I read about the insights of Professor Paul Davies in the previous posting, Looking At Cancer Through the Eyes of a Physical Scientist, Stop thinking cancer as a disease! I don’t think we need to cure cancer.

I must admit I don’t know if I am happy or I am angry after reading all these. Perhaps a mixture of both.

I am happy, because I thought the experts have decided to wake up and they don’t want to be insane (as defined above) anymore. For the past many decades the cancer problem was handled by “experts” who make things more complex and violent. And the result was dismal. Then not too long ago, someone important decided that perhaps non-cancer experts could provide a better solution to the present day cancer problem. They have decided that it is time to see things from outside the box. For that, I am real glad.

Why was I angry at the same time? If you hear stories day in and day out that people don’t get better because of someone else’s “insanity” you cannot help but become angry – why does the world allow or even encourage such a thing to happen? I don’t have to answer that question! Some patients know why.

And to make things even worse, alternative healers  who propose something “effective” but outside the norm or prevailing paradigm are labeled as quacks or snake oil peddlers.

In this second posting, I ask this question: is the present day cancer treatment based on faulty and inadequate science? I don’t have to answer that question either. Here are some research papers that I came across. Bear with me if you find it difficult to understand the jargons used and the ideas beside the reports.

In a paper, Cancer treatment as a game published in Physical Biology, 2012, Paul Orlando et al wrote:

• Chemotherapy for metastatic cancer commonly fails due to evolution of drug resistance in tumor cells.
• We view cancer treatment as a game in which the oncologists choose a therapy and tumors ‘choose’ an adaptive strategy.

Read more: http://iopscience.iop.org/1478-3975/9/6/065007/article

In a paper by Ariosto Silva et al (Cancer Res; 72(24); 6362–70. 2012.)

• Many cancers adapt to chemotherapeutic agents by upregulating membrane efflux pumps that export drugs from the cytoplasm, but this response comes at an energetic cost. Chemoresistant cells must consume excess resources to maintain resistance mechanisms.
• In breast cancer patients, expression of these pumps is low in tumors before therapy but increases after treatment.
  • The authors proposed a new method of treatment which they called “adaptive therapy.” They wrote: “Our findings challenge the existing flawed paradigm of maximum dose treatment, a strategy that inevitably produces drug resistance.”

Source: http://cancerres.aacrjournals.org/content/72/24/6362.abstract)

What is adaptive therapy?

• At the moment, the future of cancer research seems to be centered in the field of targeted chemotherapy. However, it is evident that currently neither conventional nor targeted chemotherapies will suffice against resilient tumors. 

• Conventional therapies generally aim for maximum cell death in the shortest amount of time using fixed regimens of drugs designed to eliminate as much of the tumor mass as possible under tolerable levels of toxicity to the patient. 

• However, our perception of cancer has begun to change. It is becoming increasingly evident that an individual’s cancer can be viewed as a Darwinian ecosystem containing a heterogeneous mixture of genetically distinct cancer cell types that compete amongst each other for space and resources. 

• This competition, combined with conditions within the tumor micro-environment and cancer phenotypes conducive to increased DNA damage, stimulate the rapid evolution of tumor lineages. Unfortunately, this often renders current therapies ineffective against highly adaptable cancers that quickly develop resistant cell types. 

•  Adaptive Therapy, a relatively new field of cancer treatment, has the potential to counteract cancer’s ability to adapt. 

• When intensive drug regimens are applied, the competition pressure of the chemosensitive cells is removed. This allows the resistant cells to proliferate freely, essentially dooming the patient. 

• An adaptive approach would take advantage of this discrepancy in fitness to hold the overall population of cancer cells at a low constant, avoiding the possibility of tumors consisting entirely of resistant cells. Essentially, the ultimate goal of adaptive therapy would be to manage a tumor mass efficiently by administering drugs in a dynamic regimen tailored to each individual cancer, thereby allowing the patient to effectively outlive the cancer by managing its growth over time.

Source: http://islaslab.blogspot.com/2011/05/cancer-management-through-adaptive.html

In another paper, Adaptive therapy (Cancer Research, 69:4894-903,2009) Gatenby et al. wrote:

• A number of successful systemic therapies are available for treatment of disseminated cancers. However, tumor response is often transient, and therapy frequently fails due to emergence of resistant populations. The latter reflects the temporal and spatial heterogeneity of the tumor microenvironment as well as the evolutionary capacity of cancer phenotypes to adapt to therapeutic perturbations.
• Although cancers are highly dynamic systems, cancer therapy is typically administered according to a fixed, linear protocol.
• If resistant populations are present before administration of therapy, treatments designed to kill maximum numbers of cancer cells remove this inhibitory effect and actually promote more rapid growth of the resistant populations.
• We present an alternative approach in which treatment is continuously modulated to achieve a fixed tumor population. The goal of adaptive therapy is to enforce a stable tumor burden by permitting a significant population of chemosensitive cells to survive so that they, in turn, suppress proliferation of the less fit but chemoresistant subpopulations. 

In a paper, Physics of cancer – the impact of heterogeneity, Annual Review of Condensed Matter Physics, Vol. 3: 363-382, 2012, Qiucen Zhang and Robert Austin wrote:

• It is a common mistake to view cancer as a single disease with a single possible cure which we have just not found yet.
• In reality cancer takes on many forms that share a common symptom: uncontrolled cell growth and successful invasion of cancer colonies to remote regions of the body.
• The key reason why we may never be able to defeat cancer may lie in the extreme heterogeneity of the population of the cells in a tumor: there is no one magic bullet.
• All malignant cancers… are fundamentally governed by Darwinian dynamics.
• The process of carcinogenesis requires genetic instability and highly selective local microenvironments, the combination of which promotes somatic evolution.
• These microenvironmental forces, specifically hypoxia (low oxygen conditions), acidosis and reactive oxygen species, are not only highly selective, but are also able to induce genetic instability.
• As a result, malignant cancers are dynamically evolving clades of cells living in distinct microhabitats that almost certainly ensure the emergence of therapy-resistant populations.
• Cytotoxic cancer therapies also impose intense evolutionary selection pressures on the surviving cells and thus increase the evolutionary rate. 

Gillies et al ( Nat Rev Cancer. 12: 487-93, 2012) in their paper Evolutionary dynamics of carcinogenesis and why targeted therapy does not work.

Eric Schuur in his blog post Time to Rethink Cancer Therapy? on 28 November 2012 wrote:

• The feeling of frustration in chasing cancer up the path only to have it resurrect out of seemingly nowhere still further upstream is a signal to me. I have sensed in this frustration a signal to think about cancer pathogenesis and treatment in new ways, like I’m sure others have.
• Recently I have been gratified to hear a number of researchers propose new views of what cancer is and new strategies for treating it.
• I have been a member of a tumor microenvironment interest group for a while, mostly to keep an ear to the ground in that area. Having spent many years trying to grow cancer cells in various ways, it is clear to me that they depend heavily on their microenvironment to survive.
• I noticed a few publications suggesting that resistance to chemical therapy may be mediated by more than just the response of the tumor cells. These studies suggest that the tumor microenvironment may provide protection from anti-cancer agents by secreting of growth factors from stromal cells intermingled with the tumor cells.
• In one study, WNT16B growth factor secretion was induced in stromal fibroblasts, which in turn protected the cancer cells from programmed cell death.
• Rethinking cancer therapy has been proposed by Robert Gatenby and colleagues for some time.

Source:  http://mendelspod.com/blog/time-to-rethink-cancer-therapy#sthash.EvaA1gqw.dpbs

Comments

Let me briefly summarise what these researchers said.

1. Chemotherapy for metastatic cancer commonly fails due to evolution of tumour cells to become  drug resistant.

2. So going to the oncologist is like playing a game .. the oncologists choose a therapy and the tumors ‘choose’ an adaptive strategy. A famous Singapore oncologist put it in a different way – It is just like buying a lottery hoping to strike a jackpot!

3. When chemo drugs are pumped into you, the cancer cells work overtime to pump out the drugs from their cells. If no chemo drugs were applied, the pump activity was low. This activity increased after chemo treatment. Increased activity means the cells need more energy – will this not make your MORE sick?

4. The researchers said that the commonly practised maximum-dose-shoot-to-kill treatment is flawed.  Oncologists have been doing this for years. And the patients are made to believe that the stronger the dosage of poison used the higher the chances of  “cure.” And that practice has now been challenged!

5. Now there is a new buzz word —  the future of cancer research seems to be centered in the field of targeted chemotherapy.  Take note of the terminology used nowadays, Targeted Therapy! However, it is evident that currently neither conventional nor targeted chemotherapies will suffice against resilient tumors. Target therapy make a lot of money but for patients I don’t see much meaningful results. Very often, we see disappointment. Why?

6. The researchers provide the answer:  tumor response is often transient, and therapy frequently fails due to emergence of resistant populations. Why are they resistant to the chemo-drugs? The latter reflects the temporal and spatial heterogeneity of the tumor microenvironment as well as the evolutionary capacity of cancer phenotypes to adapt to therapeutic perturbations.

7. Is the kill-all-cancer-cells strategy that is done today the correct approach? Not so. You don’t have to kill all the cancer cells in your body. The goal of adaptive therapy is to enforce a stable tumor burden by permitting a significant population of chemosensitive cells to survive so that they, in turn, suppress proliferation of the less fit but chemoresistant subpopulations.

8. It is a common mistake to view cancer as a single disease with a single possible cure which we have just not found yet. The key reason why we may never be able to defeat cancer may lie in the extreme heterogeneity of the population of the cells in a tumor: there is no one magic bullet.

9. The process of cancer that occurs in your body requires genetic instability and highly selective local microenvironments, the combination of which promotes somatic evolution. Hypoxia (low oxygen conditions), acidosis and reactive oxygen species … are also able to induce genetic instability. Don’t blame it all on only the  genes. You don’t have to remove your two beautiful breasts trying to prevent cancer! O, poor actress? There are MORE to it than just the genes.

10. Malignant cancers are dynamically evolving … living in distinct microhabitats that almost certainly ensure the emergence of therapy-resistant populations. Cytotoxic cancer therapies also impose intense evolutionary selection pressures on the surviving cells and thus increase the evolutionary rate. Take note, cytotoxic cancer therapies also contribute to this problem! You don’t cure cancer – you make cancer – with chemotherapy!

11. At long last, someone –  Eric Schuur in his blog post said: Time to Rethink Cancer Therapy? Having spent many years trying to grow cancer cells in various ways, it is clear to me that they depend heavily on their microenvironment to survive. Cancer treatment is not just about KILLING cancer cells. There is more to this!

12. If there is one message you need to know, here it is: Chemotherapy Spreads Cancer and Makes It More Aggressive.  (Click link to read more.)

If you have appetite for more, read my next post: Quotations from: NEVER FEAR CANCER AGAIN.