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乳腺癌中的多西他赛耐药性:当前见解与未来方向

Docetaxel Resistance in Breast Cancer: Current Insights and Future Directions.

作者信息

Postigo-Corrales Fátima, Beltrán-Videla Asunción, Lázaro-Sánchez Antonio David, Hurtado Ana María, Conesa-Zamora Pablo, Arroyo Ana Belén, Luengo-Gil Ginés

机构信息

Health Sciences Faculty, Universidad Católica de Murcia (UCAM), 30107 Guadalupe, Spain.

Group of Molecular Pathology and Pharmacogenetics, Pathology and Clinical Analysis Department, Instituto Murciano de Investigación Biosanitaria (IMIB), Hospital General Universitario Santa Lucía, 30202 Cartagena, Spain.

出版信息

Int J Mol Sci. 2025 Jul 23;26(15):7119. doi: 10.3390/ijms26157119.

Abstract

Docetaxel is a chemotherapeutic agent widely used for breast cancer treatment; however, its efficacy is often limited by drug resistance and associated toxicity. This review examines the molecular mechanisms of docetaxel resistance in breast cancer and discusses research advances and future directions for overcoming this challenge. Key resistance mechanisms include alterations in drug targets (microtubules), increased drug efflux, suppression of apoptosis, activation of survival signalling pathways, epithelial-to-mesenchymal transition (EMT), and cancer stem cell enrichment. An evolutionary perspective distinguishes between intrinsic and acquired resistance, emphasising the need for adaptive therapeutic strategies. Recent advances in genomic profiling, non-coding RNA research, novel drug combinations, and biomarker-guided therapies have also been reviewed. Emerging approaches, such as targeting the tumour microenvironment, harnessing immunotherapy, and implementing adaptive dosing schedules, have been discussed. This review emphasises the understanding of resistance as a multifactorial phenomenon that requires multipronged interventions. Research has aimed to identify predictive biomarkers, develop targeted agents to reverse resistance, and design rational combination strategies to improve patient outcomes. Progress in deciphering and targeting docetaxel resistance mechanisms holds promise for enhancing treatment responses and extending survival in patients with breast cancer.

摘要

多西他赛是一种广泛用于乳腺癌治疗的化疗药物;然而,其疗效常常受到耐药性和相关毒性的限制。本综述探讨了乳腺癌中多西他赛耐药的分子机制,并讨论了克服这一挑战的研究进展和未来方向。关键的耐药机制包括药物靶点(微管)改变、药物外排增加、细胞凋亡抑制、生存信号通路激活、上皮-间质转化(EMT)以及癌症干细胞富集。从进化角度区分了固有耐药性和获得性耐药性,强调了采用适应性治疗策略的必要性。还综述了基因组分析、非编码RNA研究、新型药物联合以及生物标志物导向治疗等方面的最新进展。讨论了一些新兴方法,如靶向肿瘤微环境、利用免疫疗法以及实施适应性给药方案。本综述强调将耐药性理解为一种需要多方面干预的多因素现象。研究旨在识别预测性生物标志物、开发逆转耐药性的靶向药物以及设计合理的联合策略以改善患者预后。在解读和靶向多西他赛耐药机制方面取得的进展有望提高乳腺癌患者的治疗反应并延长生存期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7972/12346647/99721bda7fa4/ijms-26-07119-g001.jpg

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