In the mid 1980s, it became apparent to me that cancer did not result from uncontrolled cell proliferation, but instead from the lack of cell death.
Yet, cancer research labored for almost a century under the erroneous belief that cancer represented dysregulation of cell proliferation.
Today, we confront another falsehood: the complexities and redundancies of human tumor biology can be easily characterized based on genomic analyses.
The process of carcinogenesis reflects the accumulation of cellular changes that provide a selective survival advantage to transformed cells. However, the intricate circuitry that provide these survival advantages, reflect harmonic osolations between DNA, RNA and protein.
Put simply, Genotype does not equal Phenotype.
It is the phenotype that determines biological behavior and clinical response in cancer. Thus, it is overly simplistic to imagine that a DNA profile by itself can provide more than a fraction of the information required to make individual patient treatment decisions.
Colon cancer
When therapies are based on genomic analysis, only a portion of the patient’s profile is taken into consideration.
These analyses disregard the environmental, epigenetic and proteomic factors that make each of us individuals. Though useful prognostically and applicable in select circumstances where a unique genetic perturbation leads to a clinical response (c-ABL and Imatinib response in CML), genomic analyses provide only a veneer of information.
The Rational Therapeutics (now Nagourney Cancer Institute) Ex Vivo Analysis – Programmed Cell Death™ (EVA-PCD) assay focuses upon the complexity of human tumors by measuring cell death, the end result of all cellular mechanisms of response and resistance acting in concert.
By incorporating cell-cell, vascular, stromal and inflammatory elements into the tumor response assessment, the EVA-PCD platform provides a robust surrogate for human tumor response. While much of modern cancer research pursues the question of “Why” cancer arises, the clinical oncologist must confront the more practical question of “How” the best outcome can be achieved.
Assay-directed therapy is truly personalized cancer care providing treatments unique to the individual.
Reblogged from February 2010.
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