Oncogenic signaling of MEK5-ERK5

• MAPKs regulate diverse cellular processes including proliferation, cell survival, differentiation, and apoptosis.
• The MEK5-ERK5 cascade has emerged as an important mediator of tumorigenesis and metastatic progression.
• These studies implicate the MEK5-ERK5 pathway as a fundamental component of drug resistance in cancer therapy.

Mitogen-activated protein kinases (MAPKs) regulate diverse cellular processes including proliferation, cell survival, differentiation, and apoptosis. While conventional MAPK constituents have well-defined roles in oncogenesis, the MEK5 pathway has only recently emerged in cancer research. In this review, we consider the MEK5 signaling cascade, focusing specifically on its involvement in drug resistance and regulation of aggressive cancer phenotypes. Moreover, we explore the role of MEK5/ERK5 in tumorigenesis and metastatic progression, discussing the discrepancies in preclinical studies and assessing its viability as a therapeutic target for anti-cancer agents.