Targeting molecular subtypes in solid cancers: successes and failures

Abstract

Purpose of review: We herein review some of the major patterns of resistance and lessons learned from the use of earlier targeted therapies in two genotype-driven solid tumors.

Recent findings: Targeted agents have rapidly expanded in the field of oncology over the past 2 decades. The breakthroughs achieved by these agents have been, however, hindered by the inevitable development of drug resistance. Intrinsic or acquired mechanisms of resistance eventually lead to treatment tolerance and tumoral plasticity with phenotypic switch and evasion of the original targeted pathway. Failures in such therapies also result from poor selectivity of the target, drug delivery, and unaffordable costs.

Summary: Based on above findings, collaborative efforts are advancing at the molecular level to design better drugs or combinatorial strategies and to develop more sensitive assays to monitor responses and the emergence of resistance.