Molecular Tests for the Choice of Cancer Therapy.

Abstract

There are over a dozen of approved cancer drugs, whose administration is tailored to predictive laboratory tests. The examples include estrogen and progesterone receptor status determination for the use of endocrine therapy, HER2 assessment for the administration of HER2-targeting agents, EGFR and ALK gene testing for lung cancer treatment, BRAF analysis in melanoma, etc. While first predictive tests relied on relatively easy laboratory procedures, more recent developments require rather sophisticated assays. For example, administration of PARP inhibitors is tailored to a comprehensive testing of BRCA1 and BRCA2 genes, and is likely to be supplemented in the future by even more systematic assessment of DNA repair pathways. The detection of an androgenindependent splice-variant of androgen-receptor (AR-V7) in castration-resistant prostate cancer is achieved through the isolation of circulating tumor cells (CTCs). The efficacy of immune check-point inhibitors correlates with the overall mutational tumor load, therefore the companion diagnostic assays may involve genome-wide scanning. Integration of next-generation sequencing (NGS) into clinical oncology is expected to boost the use of predictive tests in the forthcoming years.