March 27, 2013 Leave a comment
In his brilliant 1998 book, Consilience, Edward O. Wilson, notes: “The cost of scientific advance is the humbling recognition that reality was not constructed to be easily grasped by the human mind.”
This sententious point has remained a guiding principle in my thinking about human cancer. It is critically important for scientific investigators to be humble. We are explorers in a field more complex than any man-made system. We must be instructed by biology – as biological events will always find a way to outsmart our best efforts to explain them.
I was reminded of E.O. Wilson, when a colleague forwarded a recent publication from Molecular Cancer Therapy, “Molecular Profiling of Patient with Colorectal Cancer and Matched Targeted Therapy in Phase I Clinical Trials,” Dienstmann, R. et al MOL CANCER THER Sept 2012. The study conducted by the Molecular Therapeutics Research Unit at Vall d’Hebron Institute of Oncology in Barcelona, Spain, evaluated 254 patients for evidence of specific genetic aberrations. Their genomic analyses included, KRAS, BRAF, PIK3CA, PTEN, and pMET. Patients were then provided clinical therapy trials that matched the targeted agents (drugs with activity against the specific mutation) with their individual mutation profiles
In all, 68 patients received treatment constituting a total of 82 different molecularly targeted therapies. The clinical response rate for this population of patients who received molecularly selected therapy was 1.2%. No that isn’t a typo; it was really one point two percent.
While I applaud the scientific concept of this trial and must admit that I might have expected a somewhat higher response rate, I am not surprised by the result. In keeping with E. O. Wilson’s quote, human biology is not a puzzle designed to be solved by humans; it is instead the complex product of a billion years of evolution. Rather than demanding that cancer patients respond to those treatments we have selected for them based on genetic information, we should be instructed by the tumor’s behavior of each patient and use those insights to select amongst active drugs, whatever genetic elements they may have been originally designed to target. In my lectures, I describe this approach as the wisdom of whole cell experimental models.
I am continually humbled by the complexity of human tumor biology and delighted to have the insights that my patient’s cancer cells provide through the functional profile created by our EVA-PCD assay. Not only do I gain exciting scientific knowledge, but my patients have very good responses to the drugs we select. Not a bad day’s work.