Review

人类癌症中的药物耐药性——机制与意义

Drug resistance in human cancers - Mechanisms and implications

DOI 原文链接

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LIFE SCIENCES

影响因子:5.1

分区:医学3区 / 药学2区医学：研究与实验3区

发表日期:2024 Sep 01

作者: Sudikshaa Vijayakumar, Raveena Dhakshanamoorthy, Akshaya Baskaran, B Sabari Krishnan, Ravi Maddaly

DOI: 10.1016/j.lfs.2024.122907

摘要

癌症具有复杂的病因，除了社会经济影响外，在公共卫生角度也造成了重大影响。癌症带来的巨大挑战可以从临床试验中获得的治疗潜力有限得到理解，相较于其他疾病，癌症的治疗潜力较低。手术、化疗和放疗仍然是癌症的主要治疗手段。在这些治疗方法面临的挑战中，化疗药物诱导的耐药性可能是预后差和治疗无效的最主要原因。药物耐药性几乎表现于所有癌症类型，包括癌腺癌、白血病、骨髓瘤、肉瘤和淋巴瘤。诱导药物耐药的机制包括肿瘤微环境中的因素、参与药物代谢的基因突变、表面药物受体变化以及药物外排增加。本文全面介绍了癌症中的药物耐药及其机制。此外，除了常用化疗药物的耐药外，还探讨了抗单克隆抗体等新一代治疗药物的耐药诱导。最后，我们讨论了理解药物耐药机制的实验方法及减缓耐药诱导的潜在策略。

Abstract

Cancers have complex etiology and pose a significant impact from the health care perspective apart from the socio-economic implications. The enormity of challenge posed by cancers can be understood from the fact that clinical trials for cancer therapy has yielded minimum potential promises compared to those obtained for other diseases. Surgery, chemotherapy and radiotherapy continue to be the mainstay therapeutic options for cancers. Among the challenges posed by these options, induced resistance to chemotherapeutic drugs is probably the most significant contributor for poor prognosis and ineffectiveness of the therapy. Drug resistance is a property exhibited by almost all cancer types including carcinomas, leukemias, myelomas, sarcomas and lymphomas. The mechanisms by which drug resistance is induced include the factors within the tumor microenvironment, mutations in the genes responsible for drug metabolism, changes in the surface drug receptors and increased drug efflux. We present here comprehensively the drug resistance in cancers along with their mechanisms. Also, apart from resistance to regularly used chemotherapeutic drugs, we present resistance induction to new generation therapeutic agents such as monoclonal antibodies. Finally, we have discussed the experimental approaches to understand the mechanisms underlying induction of drug resistance and potential ways to mitigate induced drug resistance.