Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Oncogene. 2021 Nov;40(46):6395-6405. doi: 10.1038/s41388-021-02055-2. Epub 2021 Oct 13.
Platinum-based chemotherapy, including cisplatin, carboplatin, and oxaliplatin, is prescribed to 10-20% of all cancer patients. Unfortunately, platinum resistance develops in a significant number of patients and is a determinant of clinical outcome. Extensive research has been conducted to understand and overcome platinum resistance, and mechanisms of resistance can be categorized into several broad biological processes, including (1) regulation of drug entry, exit, accumulation, sequestration, and detoxification, (2) enhanced repair and tolerance of platinum-induced DNA damage, (3) alterations in cell survival pathways, (4) alterations in pleiotropic processes and pathways, and (5) changes in the tumor microenvironment. As a resource to the cancer research community, we provide a comprehensive overview accompanied by a manually curated database of the >900 genes/proteins that have been associated with platinum resistance over the last 30 years of literature. The database is annotated with possible pathways through which the curated genes are related to platinum resistance, types of evidence, and hyperlinks to literature sources. The searchable, downloadable database is available online at http://ptrc-ddr.cptac-data-view.org .
铂类化疗药物，包括顺铂、卡铂和奥沙利铂，被开给所有癌症患者的 10-20%。不幸的是，相当数量的患者会出现铂类耐药，这是临床结果的决定因素。为了理解和克服铂类耐药，已经进行了广泛的研究，耐药机制可以分为几大类生物学过程，包括（1）药物进入、排出、积累、隔离和解毒的调节，（2）增强对铂类诱导的 DNA 损伤的修复和耐受，（3）细胞存活途径的改变，（4）多效过程和途径的改变，以及（5）肿瘤微环境的改变。作为癌症研究界的资源，我们提供了一个全面的概述，并附有一个经过人工整理的数据库，其中包含了过去 30 年文献中与铂类耐药相关的 >900 个基因/蛋白。该数据库通过可能的途径注释了整理后的基因与铂类耐药的关系、证据类型，并提供了文献来源的超链接。可搜索、可下载的数据库可在 http://ptrc-ddr.cptac-data-view.org 上获得。
