Department of Biotechnology, Institute of Applied Sciences & Humanities, GLA University, Mathura, 281406, India.
Department of Biotechnology, Gautam Buddha University, Greater Noida, Uttar Pradesh, India.
Curr Drug Metab. 2024;25(4):235-247. doi: 10.2174/0113892002312369240703102215.
One of the biggest obstacles to the treatment of diseases, particularly serious conditions like cancer, is therapeutic resistance. The process of drug resistance is influenced by a number of important variables, including MDR genes, drug efflux, low-quality medications, inadequate dosage, etc. Drug resistance must be addressed, and new combinations based on the pharmacokinetics/pharmacodynamics (PK-PD) characteristics of the partner pharmaceuticals must be developed in order to extend the half-lives of already available medications. The primary mechanism of drug elimination is hepatic biotransformation of medicines by cytochrome P450 (CYP) enzymes; of these CYPs, CYP3A4 makes up 30-40% of all known cytochromes that metabolize medications. Induction or inhibition of CYP3A4-mediated metabolism affects the pharmacokinetics of most anticancer drugs, but these details are not fully understood and highlighted because of the complexity of tumor microenvironments and various influencing patient related factors. The involvement of CYPs, particularly CYP3A4 and other drug-metabolizing enzymes, in cancer medication resistance will be covered in the current review.
治疗疾病，尤其是癌症等严重疾病的最大障碍之一是治疗耐药性。耐药性的形成受到许多重要变量的影响，包括多药耐药基因、药物外排、药物质量差、剂量不足等。为了延长现有药物的半衰期，必须解决耐药性问题，并根据伙伴药物的药代动力学/药效学（PK-PD）特征开发新的组合。药物消除的主要机制是细胞色素 P450（CYP）酶对药物的肝生物转化；在这些 CYP 中，CYP3A4 占代谢药物的所有已知细胞色素的 30-40%。CYP3A4 介导的代谢的诱导或抑制会影响大多数抗癌药物的药代动力学，但由于肿瘤微环境的复杂性和各种影响患者的相关因素，这些细节还不完全清楚和突出。本文将综述 CYP，特别是 CYP3A4 和其他药物代谢酶在癌症药物耐药性中的作用。
