Having several people in my extended family stricken with one form of cancer or another, I was more than a little interested in speaking with Dr. Marco Gerlinger at the Cancer Research UK London Research Institute about his renal cancer studies. In the midst of a clinical trial evaluating a second-line drug as a potential first line therapy, his team discovered something about renal tumors. Exome sequencing of several renal tumors showed that morphological heterogeneity seen for years by pathologists is driven by profound genetic diversity.
Figure 2 of his paper is sobering. The phylogenic tree for one tumor showed that less than 34% of all mutations detected by multiregional sequencing were present in all sections of the tumor. More disheartening was that when the tumors from four different renal cancer patients were compared, less than one-third of the mutations were ubiquitously present. Biomarker research and the development of personalized cancer treatments took a hit with these findings.
But with science, when one door closes, another usually opens. The silver lining of Dr. Gerlinger’s study is an awareness that better sampling and sequencing strategies are needed to discover the full genetic diversity of tumors, and that the best first-line therapies should attack tumor gene targets in the trunk of the phylogenic tree. It’s another example that the path leading to better cancer treatments won’t always be a straight line.