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癌症化疗耐药性:最新挑战与未来思考。

Cancer Chemoresistance; Recent Challenges and Future Considerations.

机构信息

Pharmacology and Toxicology Section, University of Veterinary and Animal Sciences, Lahore, Jhang Campus, Jhang, 35200, Pakistan.

Microbiology Section, University of Veterinary and Animal Sciences, Lahore, Jhang Campus, Jhang, 35200, Pakistan.

出版信息

Cancer Treat Res. 2023;185:237-253. doi: 10.1007/978-3-031-27156-4_12.

Abstract

Cancer remains one of the serious health hazards and major causes of human mortality across the world. Despite the development of many typical antineoplastic drugs and introduction of novel targeted agents, chemoresistance constitutes a major challenge in the effective therapeutic management of cancer. Drug inactivation, efflux of anticancer agents, modification of target sites, enhanced repair of DNA damage, apoptosis failure and induction of epithelial-mesenchymal transition are the principal mechanisms of cancer chemoresistance. Moreover, epigenetics, cell signaling, tumor heterogeneity, stem cells, microRNAs, endoplasmic reticulum, tumor microenvironment and exosomes have also been implicated in the multifaceted phenomenon of anticancer drug resistance. The tendency of resistance is either intrinsically possessed or subsequently acquired by cancerous cells. From clinical oncology standpoint, therapeutic failure and tumor progression are the most probable consequences of cancer chemoresistance. Combination therapy can help to overcome the issue of drug resistance, and therefore, the development of such treatment regimens is recommended for counteracting the emergence and dissemination of cancer chemoresistance. This chapter outlines the current knowledge on underlying mechanisms, contributory biological factors and likely consequences of cancer chemoresistance. Besides, prognostic biomarkers, diagnostic methods and potential approaches to overcome the emergence of antineoplastic drug resistance have also been described.

摘要

癌症仍然是全球范围内严重的健康危害和主要死亡原因之一。尽管开发了许多典型的抗肿瘤药物并引入了新型靶向药物,但化疗耐药性仍是癌症有效治疗管理的主要挑战。药物失活、抗癌药物外排、靶位修饰、DNA 损伤修复增强、细胞凋亡失败和上皮-间充质转化的诱导是癌症化疗耐药性的主要机制。此外,表观遗传学、细胞信号转导、肿瘤异质性、干细胞、microRNAs、内质网、肿瘤微环境和外泌体也与抗肿瘤药物耐药性的多方面现象有关。耐药性的倾向要么是癌细胞固有的,要么是随后获得的。从临床肿瘤学的角度来看,治疗失败和肿瘤进展是癌症化疗耐药性的最可能后果。联合治疗可以帮助克服耐药性问题,因此,建议开发这种治疗方案来对抗癌症化疗耐药性的出现和传播。本章概述了癌症化疗耐药性的潜在机制、促成生物学因素和可能后果的最新知识。此外,还描述了预后生物标志物、诊断方法和克服抗肿瘤药物耐药性出现的潜在方法。

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