Mechanisms of intrinsic and acquired resistance to kinase-targeted therapies

作者：Bagrodia Shubha; Smeal Tod; Abraham Robert T^*

来源：Pigment Cell & Melanoma Research, 2012, 25(6): 819-831.

DOI：10.1111/pcmr.12007

• kinase inhibitors
• drug resistance
• oncogenic drivers

Cancer drugs that target pivotal signaling molecules required for malignant cell survival and growth have demonstrated striking antitumor activities in appropriately selected patient populations. Unfortunately, however, therapeutic responses are often of limited duration, typically 612months, because of emergence of drug-resistant subclones of tumor cells. In this review, we highlight several of the mechanisms of emergent resistance to several kinase-targeted small molecule therapies used in melanoma, non-small cell lung cancer (NSCLC) and other solid tumors as illustrative examples. We discuss the implications of these findings for the development of new treatment strategies to delay or prevent the onset of drug resistance.

• 出版日期2012-11