ArticlePharmaceuticals (Basel, Switzerland)2024
Computational Modeling to Identify Drugs Targeting Metastatic Castration-Resistant Prostate Cancer Characterized by Heightened Glycolysis.
Article in Pharmaceuticals (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Article
- Identification and validation of mitochondrial transport and glycolysis-associated prognostic and therapeutic target for lung adenocarcinoma patients.Frontiers in genetics · 2026Article
- Clinical potential and experimental validation of prognostic genes in hepatocellular carcinoma revealed by risk modeling utilizing single cell and transcriptome constructs.Frontiers in immunology · 2025Article
- Application of network pharmacology in synergistic action of Chinese herbal compounds.Theory in biosciences = Theorie in den Biowissenschaften · 2024Review
- Identification of Anticancer Enzymes and Biomarkers for Hepatocellular Carcinoma through Constraint-Based Modeling.Molecules (Basel, Switzerland) · 2024Article
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Authors and funding
7 authors.
Funding
Abstract
Metastatic castration-resistant prostate cancer (mCRPC) remains a deadly disease due to a lack of efficacious treatments. The reprogramming of cancer metabolism toward elevated glycolysis is a hallmark of mCRPC. Our goal is to identify therapeutics specifically associated with high glycolysis. Here, we established a computational framework to identify new pharmacological agents for mCRPC with heightened glycolysis activity under a tumor microenvironment, followed by in vitro validation. First, using our established computational tool, OncoPredict, we imputed the likelihood of drug responses to approximately 1900 agents in each mCRPC tumor from two large clinical patient cohorts. We selected drugs with predicted sensitivity highly correlated with glycolysis scores. In total, 77 drugs predicted to be more sensitive in high glycolysis mCRPC tumors were identified. These drugs represent diverse mechanisms of action. Three of the candidates, ivermectin, CNF2024, and P276-00, were selected for subsequent vitro validation based on the highest measured drug responses associated with glycolysis/OXPHOS in pan-cancer cell lines. By decreasing the input glucose level in culture media to mimic the mCRPC tumor microenvironments, we induced a high-glycolysis condition in PC3 cells and validated the projected higher sensitivity of all three drugs under this condition (
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