Tumor cell chemoresistance

Tumor cell chemoresistance is a multifaceted biological phenomenon characterized by the ability of malignant cells to survive and proliferate despite the presence of chemotherapeutic drugs. This state can be intrinsic, where resistance factors are present prior to any treatment, or acquired through the selective pressure of therapy, leading to disease recurrence and treatment failure [PMC: 4281488]. The molecular basis of resistance is diverse, prominently involving the upregulation of ATP-binding cassette (ABC) transporters like ABCB1 (P-glycoprotein) and ABCG2, which actively efflux various drugs out of the cell [PubMed: 15334057]. Other key drivers include the evasion of apoptosis through the overexpression of anti-apoptotic proteins such as Bcl-2, enhanced DNA repair mechanisms (e.g., nucleotide excision repair) that fix drug-induced damage, and the protective influence of the tumor microenvironment including cancer stem cells (CSCs) [PubMed: 34465492]. While numerous drugs have been developed to inhibit specific resistance components, such as P-glycoprotein inhibitors, their clinical utility has been hampered by toxicity and the compensatory activation of alternative survival pathways.

Other names

Multi-drug resistance (MDR)Cancer drug resistanceChemotherapy resistanceAcquired drug resistanceIntrinsic drug resistance

Strategies to address this phenomenon involve the inhibition of ATP-binding cassette (ABC) transporters to prevent drug efflux, the use of BH3 mimetics to restore apoptotic sensitivity, and the inhibition of DNA repair enzymes like PARP to enhance the cytotoxic effects of DNA-damaging agents [PubMed: 28224522, PMC: 6410291].