A highly annotated database of genes associated with platinum resistance in cancer

Abstract

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.

Multiomic analysis identifies CPT1A as a potential therapeutic target in platinum-refractory, high-grade serous ovarian cancer

“…One limitation of this study is that the limited number of patients represented in the study likely does not represent all the heterogeneous mechanisms underlying clinical resistance to platinum compounds. 13 Future studies with more patients will be required to determine whether the findings in our study are generalizable to all HGSOC tumors or only specific subclasses. Additionally, our preclinical models do not capture the influence of the immune system and tumor microenvironment on platinum responsiveness.…”

“… 113 Platinum resistance is a major determinant of survival, particularly in OCs, which are frequently diagnosed at late stage. Decades of literature demonstrate that resistance is multifactorial, 12 , 13 and there has been no clinical translation of biomarkers to predict platinum response or treatments to overcome platinum resistance, and these remain unmet clinical needs. To date, no study using modern proteogenomic technologies has been undertaken to characterize cancer cell responses to platinum or to understand mechanisms of resistance.…”

“… 7 Platinum resistance is multifactorial, involving alterations in drug transporters, detoxification, removal of reactive oxygen species (ROS), DNA repair, oncogenes, metabolic reprogramming, and cell-death pathways. 8 , 9 , 10 , 11 Remarkably, despite >30 years of literature on platinum responses in human cancer, 12 , 13 none of these findings is used clinically to stratify patients for platinum resistance or exploited therapeutically to treat platinum-resistant disease.…”

Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer

“…New studies are raising more and more questions nowadays about the mechanism based on chemotherapy resistance. Researches found that the primary mechanisms of platinum resistance included drug accumulation, the ability of DNA or RNA repair efficiency, and self-detoxification of cells ( 11 ). Of those, reduction in drug accumulation is one of the most generally acknowledged mechanisms of acquired OXA resistance ( 12 ).…”

The Long Non-Coding RNA SNHG12 as a Mediator of Carboplatin Resistance in Ovarian Cancer via Epigenetic Mechanisms

“…The list of 4255 DEGs and 14,529 DMPs detected in our panel of OC cell lines was compared with the platinum response-related gene list (937 genes/proteins) recently curated by Huang et al [ 51 ]. We found 254 DEGs and 142 DMPs overlapping with the database entries ( Table S5 ).…”