FOXO3a in cancer drug resistance

Cancer is one of the major causes of death and a significant obstacle to increasing life expectancy worldwide. Chemotherapy remains the first-line adjuvant therapeutic option for all stages of cancer, and it can effectively improve patients’ prognosis in the short term. However, its long-term effect on extending patient survival is limited due to the emergence of drug resistance. The mechanisms involved in drug resistance are complicated and still not fully understood. Forkhead box class O3a (FOXO3a) belongs to the FOXO subfamily of forkhead transcription factors. It plays a crucial role in many aspects of cancer progression and drug resistance. Recent studies have shown that FOXO3a dysregulation contributes to drug resistance development through various mechanisms, including modulating oncogenic signaling pathways, evading apoptosis, promoting excessive drug efflux, inducing autophagy, facilitating epithelial to mesenchymal transition, enhancing DNA damage repair, and altering the characteristics of cancer stem cells. FOXO3a also exhibits great potential as a diagnostic and prognostic biomarker candidate and therapeutic target for cancer patients. In this review, we summarize recent findings on the roles and mechanisms of FOXO3a in cancer drug resistance and highlight its clinical implications as a biomarker and a therapeutic target in cancer treatment. •FOXO3a is widely involved in the occurrence and progression of many cancer types.•FOXO3a dysregulation contributes to the development of cancer drug resistance.•FOXO3a regulates many aspects of drug resistant cancer cells, such as cell apoptosis, drug efflux, and autophagy.•FOXO3a exhibit great potential as novel biomarker for prognostic evaluation and therapeutic target for cancer patients.