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抗癌单克隆抗体的药物遗传学

Pharmacogenetics of anticancer monoclonal antibodies.

作者信息

Shek Dmitrii, Read Scott A, Ahlenstiel Golo, Piatkov Irina

机构信息

Blacktown Clinical School, Western Sydney University, Blacktown, NSW 2148, Australia.

Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.

出版信息

Cancer Drug Resist. 2019 Mar 19;2(1):69-81. doi: 10.20517/cdr.2018.20. eCollection 2019.

Abstract

Pharmacogenetics is the study of therapeutic and adverse responses to drugs based on an individual's genetic background. Monoclonal antibodies (mAbs) are a rapidly evolving field in cancer therapy, however a number of newly developed and highly effective mAbs (e.g., anti-CTLA-4 and anti-PD-1) possess pharmacogenomic profiles that remain largely undefined. Since the first chemotherapeutic mAb Rituximab was approved in 1997 by the US Food and Drug Administration for cancer treatment, a broad number of other mAbs have been successfully developed and implemented into oncological practice. Nowadays, mAbs are considered as one of the most promising new approaches for cancer treatment. The efficacy of mAb treatment can however be significantly affected by genetic background, where genes responsible for antibody presentation and metabolism, for example, can seriously affect patient outcome. This review will focus on current anticancer mAb treatments, patient genetics that shape their efficacy, and the molecular pathways that bridge the two.

摘要

药物遗传学是基于个体遗传背景研究药物治疗反应和不良反应的学科。单克隆抗体(mAb)是癌症治疗中一个快速发展的领域,然而,许多新开发的高效单克隆抗体(如抗CTLA-4和抗PD-1)的药物基因组特征在很大程度上仍不明确。自1997年首个化疗单克隆抗体利妥昔单抗被美国食品药品监督管理局批准用于癌症治疗以来,大量其他单克隆抗体已成功开发并应用于肿瘤学实践。如今,单克隆抗体被认为是最有前景的癌症治疗新方法之一。然而,单克隆抗体治疗的疗效会受到遗传背景的显著影响,例如,负责抗体呈递和代谢的基因会严重影响患者的治疗结果。本综述将聚焦于当前的抗癌单克隆抗体治疗、影响其疗效的患者遗传学因素以及连接两者的分子途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99db/9019180/3c9a317ea3bd/cdr-2-69.fig.1.jpg

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