Abstract
Pancreatic cancer, hepatocellular carcinoma (HCC), and mesothelioma are treatment-refractory cancers, and patients afflicted with these cancers generally have a very poor prognosis. The genomics of these tumors were analyzed as part of The Cancer Genome Atlas (TCGA) project. However, these analyses are an overview and may miss pathway interactions that could be exploited for therapeutic targeting. In this study, the TCGA Pan-Cancer datasets were queried via cBioPortal for correlations among mRNA expression of key genes in the cell cycle and mitochondrial (mt) antioxidant defense pathways. Here we describe these correlations. The results support further evaluation to develop combination treatment strategies that target these two critical pathways in pancreatic cancer, hepatocellular carcinoma, and mesothelioma.
Highlights
Mesothelioma, hepatocellular carcinoma (HCC), and pancreatic cancers are three of the most devastating cancers; these diseases are recalcitrant to treatment [1,2,3]
We chose to focus on (1) pathways that have an FDA-approved drug, (2) at least one target of a two-target pair having a known association with the cancer, (3) the fact that there is a plausible interaction between genes or gene products, and (4) novel combinations
Cell cycle-related proteins and mitochondrial antioxidant defense proteins are important to the pathogenesis and growth of each of these cancers; we hypothesized that interactions may exist between these two pathways that may be amenable to targeting with agents already approved for other uses by the FDA
Summary
Mesothelioma, hepatocellular carcinoma (HCC), and pancreatic cancers are three of the most devastating cancers; these diseases are recalcitrant to treatment [1,2,3]. Potentially curative options are not available (a significant proportion of cases of mesothelioma, hepatocellular, and pancreatic cancers), systemic therapy with a targeted agent or chemotherapy are the standard treatment options [4,5,6]. The standard first-line therapy is the chemotherapy regimen cisplatin (involved in DNA adduct formation) plus the antifolate agent pemetrexed (with or without the angiogenesis inhibitor bevacizumab) [3,7]. The chemotherapy regimen called FOLFIRINOX (5-fluorouracil, oxaliplatin, and irinotecan) is associated with the highest overall survival in patients with advanced disease [9]. Two cellular pathways that are promising as targets in these cancers include (1) the cell cycle pathway and related genes/proteins and (2) mitochondrial (mt) antioxidant defense [12,13]
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