Kar Animesh, Agarwal Shivam, Singh Agrata, Bajaj Avinash, Dasgupta Ujjaini
Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India.
Amity Institute of Integrative Sciences and Health, Amity University Haryana, Panchgaon, Manesar, Gurgaon-122413, Haryana, India.
Transl Oncol. 2024 Apr;42:101901. doi: 10.1016/j.tranon.2024.101901. Epub 2024 Feb 10.
Cancer heterogeneity poses a significant hurdle to the successful treatment of the disease, and is being influenced by genetic inheritance, cellular and tissue biology, disease development, and response to therapy. While chemotherapeutic drugs have demonstrated effectiveness, their efficacy is impeded by challenges such as presence of resilient cancer stem cells, absence of specific biomarkers, and development of drug resistance. Often chemotherapy leads to a myriad of epigenetic, transcriptional and post-transcriptional alterations in gene expression as well as changes in protein expression, thereby leading to massive metabolic reprogramming. This review seeks to provide a detailed account of various transcriptional regulations, proteomic changes, and metabolic reprogramming in various cancer models in response to three primary chemotherapeutic interventions, docetaxel, carboplatin, and doxorubicin. Discussing the molecular targets of some of these regulatory events and highlighting their contribution in sensitivity to chemotherapy will provide insights into drug resistance mechanisms and uncover novel perspectives in cancer treatment.
癌症异质性对该疾病的成功治疗构成了重大障碍，并且受到遗传、细胞与组织生物学、疾病发展以及对治疗反应的影响。虽然化疗药物已证明有效，但其疗效受到诸如存在具有抗性的癌症干细胞、缺乏特异性生物标志物以及耐药性产生等挑战的阻碍。化疗常常导致基因表达发生大量表观遗传、转录和转录后改变以及蛋白质表达变化，从而引发大规模的代谢重编程。本综述旨在详细阐述在各种癌症模型中，针对三种主要化疗干预措施（多西他赛、卡铂和阿霉素）所发生的各种转录调控、蛋白质组学变化和代谢重编程。讨论其中一些调控事件的分子靶点并强调它们对化疗敏感性的贡献，将有助于深入了解耐药机制并揭示癌症治疗的新观点。
