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.
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).
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.
"...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.
Are you thinking differently?
Bonny is a data enthusiast applying curated analysis and visualization to persistent tensions between health policy, economics, and clinical research in oncology.