Clinical Translation of Cancer Genomics
The real question, now that we’ve made considerable progress, is how to make use of that information in the clinic. Many institutions have launched personalized oncology programs, which consider tumor mutation and/or gene expression profiling. Early reports suggest that 30–70% of cases will harbor mutations that are “actionable” for targeted therapy or patient stratification. The poster child for this might be the identification of BRAF as a driver gene in melanoma, which led to the use of BRAF inhibitors in melanomas that harbor the V600E mutation. It’s a wonderful story, but the simple fact is that most targeted therapies didn’t emerge from large-scale genomics studies, but from a deep understanding of specific pathways involved in defined tumor types.
Further, the successful identification (and targeted therapy against) a driver mutation in one tumor type does not guarantee it will work in another type. Other factors—tissue specificity, genetic environment, and tumor micro-environment—must be considered as well.
In many current clinical trials, gene expression and mutation data are being concomitantly assessed for insight into patient stratification and therapeutic response. These sorts of trials are necessary to close the gap between new knowledge from large-scale cancer genomics and its application in the clinic. The feedback loop needs to work both ways: Clinical trial results should inform future oncogenomics studies as well.
It’s clear that we will both creativity and cross-discipline expertise to carry the mission forward from here. Specifically, we’ll need:
Continued efforts to develop large, high-resolution, clinical-genomics datasets
Better and earlier access to drugs
Cross-discipline expertise in cancer, genomics, and informatics (“onco-bioinformaticians”)
Integration of genomic data into clinical tumor board discussions
Beating cancer is an important but incredibly difficult mission, and it won’t be solved by one scientific discipline alone. Collaborative efforts by cross-discipline teams are going to be necessary. Let’s get going.