Counterpoint: Successes in the Pursuit of Precision Medicine: Biomarkers Take Credit

Recent years have ushered in technologies that have transformed our ability to interrogate the underlying abnormalities in individual tumors, including next-generation genomic sequencing, transcriptomics, and proteomics. As a result, numerous actionable molecular targets have emerged. There are currently >70 targeted agents FDA approved for the treatment of solid and hematologic malignancies, and the numbers continue to increase (http://www.mycancergenome.org/content/molecular-medicine/overview-of-targeted-therapies-for-cancer/). Further, immunotherapy has arisen as a new type of targeted therapeutic that specifically reactivates the immune system based on knowledge of checkpoints. Once reactivated, the immune system differentiates tumor cells from normal elements based on the neoantigens presented by the cancer cells as a result of the mutanome. Hence, the fields of genomics and immunotherapy, considered the pillars of precision medicine, are wedded to each other.

In his commentary elsewhere in this issue (page 859), Gyawali asks why an approach as attractive as precision medicine has failed to improve outcomes. He then proceeds to postulate the following explanations for this presumed failing: (1) the concept of precision medicine may be fallacious, and (2) the biomarkers used are inadequately validated. For the latter, he uses the examples of ERCC1 as a predictor of response to platinum agents and PD-L1 as a predictor of response to anti–PD-1/PD-L1 checkpoint inhibitors.

Herein, we will show that precision medicine has already made substantial advances and has dramatically improved outcomes in several lethal cancers. Further, there are many remarkably useful biomarkers for response.