Targeted drug development in melanoma and nonsmall cell lung cancer: BRAF, MEK, and ALK inhibitors

In the past few decades, many advances have been witnessed in the development of personalized molecular therapies, especially in the areas of melanoma and nonsmall cell lung cancer (NSCLC) among all other medical oncology fields. These therapies can be roughly divided into three categories at present: (1) targeting membrane-bound receptor tyrosine kinase (RTK), using either monoclonal antibodies or tyrosine kinase inhibitor (TKI), (2) targeting intracellular mitogen-activated protein kinase (MAPK) pathway, and (3) targeting intracellular phosphoinositide 3-kinase (PI3K) pathway. Currently, melanoma research focuses on MAPK pathway, spending efforts to clarify the intricate interactions in RAS-MEK-ERK-signaling cascades, whereas in the field of NSCLC, most achievements have been made targeting RTKs. This review will discuss the recent movements of drug development in these two areas, specifically BRAF and MEK inhibitors in melanoma, and ELM4-ALK inhibitors in lung cancer, along with the mechanisms of drug resistance and potential future strategies.