Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao, 266021, China; School of Basic Medical Sciences, Qingdao Medical College, Qingdao University, Qingdao, 266071, China.
School of Basic Medical Sciences, Qingdao Medical College, Qingdao University, Qingdao, 266071, China.
Cancer Lett. 2022 Aug 1;540:215724. doi: 10.1016/j.canlet.2022.215724. Epub 2022 May 8.
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.
癌症是全球死亡的主要原因之一，也是影响预期寿命延长的重大障碍。化疗仍然是所有癌症阶段的一线辅助治疗选择，它可以在短期内有效改善患者的预后。然而，由于耐药性的出现，其长期延长患者生存的效果有限。耐药性涉及的机制复杂，尚未完全了解。叉头框蛋白 O3a（FOXO3a）属于叉头转录因子 FOXO 亚家族。它在癌症进展和耐药性的许多方面发挥着关键作用。最近的研究表明，FOXO3a 失调通过多种机制导致耐药性的发展，包括调节致癌信号通路、逃避细胞凋亡、促进过度药物外排、诱导自噬、促进上皮间质转化、增强 DNA 损伤修复以及改变癌症干细胞的特性。FOXO3a 作为癌症患者的诊断和预后生物标志物候选物以及治疗靶点也具有巨大的潜力。在这篇综述中，我们总结了 FOXO3a 在癌症耐药性中的作用和机制的最新发现，并强调了其作为癌症治疗中的生物标志物和治疗靶点的临床意义。
