Figure 2. Key mechanisms implicated in emergence of platinum resistance.

OC cells develop chemoresistance due to diverse mechanisms, including paracrine release of cytokines from stromal elements in the TME, upregulation of cell membrane ABC transporters to enhance drug efflux, increased cellular antioxidant defense to reduce ROS, promotion of antiapoptotic signaling through increased expression of antiapoptotic proteins and decreased expression of death ligand receptors, metabolic reprogramming, an increase in chromatin packing, genetic and epigenetic inactivation of tumor suppressor and DNA repair genes, modulation of superenhancers that induce transcriptional reprogramming, and acquisition of mutations, including reverting BRCA 1 and 2 mutations. ABCB1, also known as P-glycoprotein (PgP) and multidrug resistance protein 1 (MDR1); ABCC1, multidrug resistance-associated protein 1 (also known as MRP1); ABCG2, breast cancer resistance protein (also known as BCRP); TRAILR1, TNF-related apoptosis-inducing ligand receptor 1; TRAILR2, TNF-related apoptosis-inducing ligand receptor 2; FAS, Fas cell surface death receptor; MADD, MAPK-activating death domain; c-FLIP, cellular FLICE-like inhibitory protein; GPX4, glutathione peroxidase 4; NRF2, nuclear factor erythroid-2 related factor; ALDH1, aldehyde dehydrogenase 1; BRCA1, breast cancer gene 1; EMT, epithelial-mesenchymal transition; RB1, retinoblastoma 1; NF1, neurofibromatosis 1; RAD51B, RAD51 paralog B.