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个性化癌症治疗:药物遗传学在克服耐药性和毒性方面的作用。

Personalizing cancer therapy: the role of pharmacogenetics in overcoming drug resistance and toxicity.

作者信息

Nafchi Hossein Mardani, Solatzadeh Hormoz, Hajimaghsoudi Elnaz, Babakhanzadeh Emad

机构信息

Department of Pharmacology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Medical Biotechnology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

出版信息

Mol Biol Rep. 2025 Aug 2;52(1):785. doi: 10.1007/s11033-025-10887-4.

Abstract

Cancer pharmacogenetics has become a cornerstone of precision oncology. It offers the potential to optimize therapeutic outcomes by tailoring treatments to individual genetic profiles. This review explores the central role of pharmacogenomics in addressing key challenges in cancer therapy, including drug resistance, variability in drug response between patients and chemotherapy-induced toxicity. We highlight key pharmacogenetic markers - such as DPYD, TPMT, UGT1A1, CYP2D6, ERCC1 and XRCC1 - that influence the metabolism, efficacy and toxicity of widely used chemotherapeutic agents. In addition, we discuss the role of ATP-binding cassette transporters (ABC transporters), including ABCB1, ABCG2 and ABCC2, in mediating drug resistance and their importance for personalized treatment strategies. Despite significant progress, the clinical translation of pharmacogenomics still faces several challenges. These include the need for large-scale validation of biomarkers in different populations, the integration of gene-environment interactions and the clarification of ethical and privacy concerns related to genetic testing. New technologies such as next-generation sequencing (NGS), liquid biopsies and artificial intelligence (AI)-based predictive models can overcome these obstacles by enabling real-time monitoring of tumor dynamics and refining personalized treatment protocols. The future of cancer pharmacogenetics lies in the integration of multi-omics data encompassing genomics, epigenomics, transcriptomics and proteomics to provide a comprehensive understanding of tumor biology and drug response. Collaboration between academic institutions, pharmaceutical companies and regulatory authorities is essential to establish standardized protocols for biomarker validation and expand pharmacogenomic databases. In addition, the development of ethical frameworks and patient-centered approaches will ensure the responsible integration of pharmacogenomics into clinical practice. By addressing current challenges and utilizing new technologies, cancer pharmacogenetics holds great promise for advancing precision oncology. This review highlights the importance of personalized medicine in improving therapeutic efficacy, minimizing adverse effects and ultimately improving patient outcomes in the fight against cancer.

摘要

癌症药物遗传学已成为精准肿瘤学的基石。它通过根据个体基因图谱定制治疗方案,为优化治疗效果提供了潜力。本综述探讨了药物基因组学在应对癌症治疗关键挑战中的核心作用,包括耐药性、患者间药物反应的变异性以及化疗诱导的毒性。我们重点介绍了影响广泛使用的化疗药物代谢、疗效和毒性的关键药物遗传学标志物,如DPYD、TPMT、UGT1A1、CYP2D6、ERCC1和XRCC1。此外,我们讨论了ATP结合盒转运蛋白(ABC转运蛋白),包括ABCB1、ABCG2和ABCC2,在介导耐药性中的作用及其对个性化治疗策略的重要性。尽管取得了重大进展,但药物基因组学的临床转化仍面临若干挑战。这些挑战包括需要在不同人群中对生物标志物进行大规模验证、整合基因-环境相互作用以及澄清与基因检测相关的伦理和隐私问题。下一代测序(NGS)、液体活检和基于人工智能(AI)的预测模型等新技术可以通过实时监测肿瘤动态和完善个性化治疗方案来克服这些障碍。癌症药物遗传学的未来在于整合包括基因组学、表观基因组学、转录组学和蛋白质组学在内的多组学数据,以全面了解肿瘤生物学和药物反应。学术机构、制药公司和监管机构之间的合作对于建立生物标志物验证的标准化方案和扩大药物基因组学数据库至关重要。此外,制定伦理框架和以患者为中心的方法将确保药物基因组学在临床实践中的负责任整合。通过应对当前挑战并利用新技术,癌症药物遗传学在推进精准肿瘤学方面具有巨大潜力。本综述强调了个性化医疗在提高治疗效果、最小化不良反应以及最终改善癌症治疗患者结局方面的重要性。

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