Cancer is biologically diverse, highly heterogeneous, and associated with molecular alterations, significantly contributing to mortality worldwide. Currently, cancer patients are subjected to single or combination treatments comprising chemotherapy, surgery, immunotherapy, radiation therapy, and targeted therapy. Chemotherapy remains the first line of treatment in cancer but faces a major obstacle in the form of chemoresistance. This obstacle has resulted in relapses and poor patient survival due to decreased treatment efficacy. Aberrant pre-mRNA alternative splicing can significantly modulate gene expression and function involved in the resistance mechanisms, potentially shaping the intricate landscape of tumour chemoresistance. Thus, novel strategies targeting abnormal pre-mRNA alternative splicing and understanding the molecular mechanisms of chemotherapy resistance could aid in overcoming the chemotherapeutic challenges. This review first highlights drug targets, drug pumps, detoxification mechanisms, DNA damage response, and evasion of apoptosis and cell death as key molecular mechanisms involved in chemotherapy resistance. Furthermore, the review discusses the progress of research on the dysregulation of alternative splicing and molecular targets involved in chemotherapy resistance in major cancer types.
癌症在生物学上具有多样性和高度异质性，且与分子改变密切相关，是全球死亡率的重要诱因。目前，癌症患者接受的治疗包括单一或联合疗法，涵盖化疗、手术、免疫治疗、放射治疗及靶向治疗。化疗仍是癌症治疗的首选方案，但面临化疗耐药这一主要障碍。由于治疗效果下降，这一障碍导致患者复发率高、生存率低。异常的前体mRNA选择性剪接可显著调控参与耐药机制的基因表达与功能，可能塑造肿瘤化疗耐药的复杂格局。因此，针对异常前体mRNA选择性剪接的新策略及对化疗耐药分子机制的理解，有助于克服化疗面临的挑战。本综述首先强调药物靶点、药物泵、解毒机制、DNA损伤反应以及凋亡和细胞死亡逃逸作为化疗耐药的关键分子机制。此外，综述还讨论了主要癌症类型中与化疗耐药相关的选择性剪接失调及分子靶点的研究进展。
Aberrant Splicing as a Mechanism for Resistance to Cancer Therapies
肿瘤(癌症)患者之家