Ancient cancer stories: are we listening?

Think about the amount of investment in R&D for cancer. The 21st Century Cures Act authorized $1.8 billion in funding over 7 years. Much of the research earmarked for the upstream social determinants of health and prevention was diverted. What is our societal return on investment?

Insights are driven from the margins. Those of us merging different industry perspectives are loaded with questions. The US National Cancer Institute (NCI) bet on these evolving questions when inviting physical scientists to join the debate identifying novel approaches to cancer etiology.

What if cancer tumors are indeed atavisms as speculated by Paul Davies? Introductory courses on embryology mention pharyngeal gill slits, rudimentary tails and other remnants of aquatic life. In the majority of instances these genes are silenced as development progresses but ancestral traits sometimes remain--these are called atavisms.

As a physicist and director of the Beyond Center for Fundamental Concepts in Science at Arizona State University, Dr. Davies suggests a theory that a disruption in silencing ancestral genes allows cancer to activate an "ancestral core" that mirrors evolution but in reverse--conferring malignant traits.

​Physics embraces the anomaly, because it understands that it is only by explaining this anomaly that science move forward. The great American physicist Richard Feynman said “The thing that doesn’t fit is the thing that’s the most interesting; the part that doesn’t go according to what you expected”. Medicine, on the other hand, rejects new theories like a prom queen rejects pimple faced suitors. If ‘The Man’ says that calories cause obesity, then all other theories are shouted down.

If ‘The Man’ says that cancer is caused by genetic mutations, then all other theories may apply elsewhere. They call this process ‘peer-review’, and glorify it as a religion. Galileo, for example, was not a fan of peer review by the church. In physics, your theory is only good if it explains the known observations. In medicine, your theory is only good if everybody else likes it, too. This explains the rapid pace of progress in the physical sciences and the glacial pace of medical research.--Dr Jason Fung

But challenging the status quo isn't for the faint of heart. Somatic mutation theories describe the random and unpredictable nature of genetic mutations but what if we can appreciate the deceptively organized behavior of cancer across a wide variety of tissue types?

Collaborations crumble when pre-ordained objectives don't hold up to intense scrutiny or verification in external databases. I was surprised how many executives and self-prescribed experts lack curiosity. I worked with a team that requested data from a pharmaceutical client's investigator's brochure--but none of the relevant content. Understanding why a client is launching a second or third to market oncology drug is vital information.

Assumptions made in the pre-clinical phase of drug development matter.

An article by a physicist and an oncologist, Stochasticity and Determinism in Cancer Creation and Progression should bring about a lively debate. Think of stochasticity as randomness and determinism as an assumption that the predictability of genes alone can explain a theoretical construct.  

Does the cancer subroutine possess a genomic fingerprint? In addressing the question of genomic changes in cancer, it is crucial to distinguish between mutations, where gene sequences change, and gene expression, where sequences are unchanged but normally silenced genes become switched on (or vice versa).

​According to the foregoing atavism explanation of cancer, gain-of-function in cancer stems mainly from the inappropriate up-regulation of intact genes rather than the accidental products of damaged genes: i.e. the cancer phenotype is primarily epigenetically rather than genetically derived. In the case of gene expression in cancer, patterns certainly exist.--Stochasticity and determinism in cancer creation and progression

I think we all try to do better. Unfortunately our Google searching brains neglect to appreciate that granularity rarely floats to the top. The easy data to access is rarely the right data.

Most descriptions of cancer progression focus on the proliferative aspect. It is well known that the tumor burden per se can usually be successfully reduced by a variety of clinical interventions—surgery, radiation and drugs—but that for metastatic cancer this approach rarely eliminates the disease completely on account of the phenotypic changes resulting in advancing malignancy. By concentrating on gain-of-function properties, such as the aforesaid proliferation, therapeutic strategies typically target cancer's strengths. But by defaulting to an ancestral phenotype, cancer cells lose more recently evolved functionality. This loss of function may represent the Achilles' heel of cancer, and therapies designed to target cancer's weaknesses may offer a more hopeful and unique alternative for the future

I am reminded by the words of a brilliant poet, David Whyte. The full poem is at the link.

​Coleman's Bed

"...Live in this place
as you were meant to and then,
surprised by your abilities,
become the ancestor of it all,
the quiet, robust and blessed Saint
that your future happiness
will always remember."
​

Here he reflects on the poem edited from Oprah's-Lifeclass.

​I have a poem called "Coleman's Bed" about a place in the West of Ireland where the Irish saint Coleman lived. The last line of that poem calls on the reader to remember "the quiet, robust and blessed saint that your future happiness will always remember." 

We go to places of pilgrimage where saints have lived, or even to Graceland, where Elvis lived, because these people gave something to the rest of us—music or good works— that has carried on down the years and that was a generous gift to the future. 

But that blessed saint could also be yourself—the person who, in this moment, makes a decision that can make a bold path into the years to come and whom your future happiness will always remember. What could you do now for yourself or others that your future self would look back on and congratulate you for—something it could view with real thankfulness because the decision you made opened up the life for which it is now eternally grateful?

Are you thinking differently?