Mehran Molavand
1,2* 
, Amir Valizadeh
1,2 , Maryam Majidinia
3 , Bahman Yousefi
1* 1 Department of clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical science, Tabriz, Iran
2 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
3 Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
Abstract
Cancer is among the leading causes of global mortality. In addition to uncontrolled proliferation, cancer cells activate survival pathways that favor the expansion of malignant cell populations. A critical component of these survival mechanisms is drug resistance, which often prevents the achievement of optimal therapeutic outcomes. At a cellular level, drug resistance arises from the modulation of multiple cellular processes, including apoptosis, DNA repair system, cancer stem cells, drug-metabolizing enzymes, and transporters. Among oncogenic signaling pathways, the MAPK/ERK cascade is frequently hyperactivated in cancer cells and serves as an upstream regulator of key effectors that drive drug resistance mechanisms. Consequently, patient profiling and therapeutic strategies aimed at targeting specific components of this pathway may not only counteract drug insufficiency but also facilitate personalized treatment approaches. This review provides an updated overview of the role of MAPK/ERK signaling in mediating drug resistance in cancer cells and discusses current and emerging therapeutic strategies, including combination therapies, pathway inhibitors, and novel drug development.