Molecular target inhibitors have been regularly approved by Food and Drug Administration (FDA) for tumor treatment

and most of them intervene in tumor cell proliferation and metabolism. The RAS–RAF–MEK–ERK pathway is a conserved signaling pathway that plays vital roles in cell proliferation

survival

and differentiation. The aberrant activation of the RAS–RAF–MEK–ERK signaling pathway induces tumors. About 33% of tumors harbor RAS mutations

while 8% of tumors are driven by RAF mutations. Great efforts have been dedicated to targeting the signaling pathway for cancer treatment in the past decades. In this review

we summarized the development of inhibitors targeting the RAS–RAF–MEK–ERK pathway with an emphasis on those used in clinical treatment. Moreover

we discussed the potential combinations of inhibitors that target the RAS–RAF–MEK–ERK signaling pathway and other signaling pathways. The inhibitors targeting the RAS–RAF–MEK–ERK pathway have essentially modified the therapeutic strategy against various cancers and deserve more attention in the current cancer research and treatment.