ArticleCancers2021
Drug Repurposing to Identify a Synergistic High-Order Drug Combination to Treat Sunitinib-Resistant Renal Cell Carcinoma.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- A systems-level machine learning approach uncovers therapeutic targets in clear cell renal cell carcinoma.npj drug discovery · 2026Article
- Renal cell carcinoma organoids for precision medicine: bridging the gap between models and patients.Journal of translational medicine · 2025Review
- Rational Design of Non-Toxic Multidrug Combinations Demonstrates Durable and Hypoxia-Enhanced Efficacy Against Renal Cell Carcinoma.Pharmaceutics · 2025Article
- Liposomal Tubacin: Strategies for the Formulation of a Highly Hydrophobic Anticancer Drug.Pharmaceutics · 2025Article
- Organoids as Sophisticated Tools for Renal Cancer Research: Extensive Applications and Promising Prospects.Cellular and molecular bioengineering · 2024Review
- Drug Repurposing of Generic Drugs: Challenges and the Potential Role for Government.Applied health economics and health policy · 2023Article
- Fine-tuning the cytotoxicity of ruthenium(II) arene compounds to enhance selectivity against breast cancers.Dalton transactions (Cambridge, England : 2003) · 2023Article
- Ketorolac modulates Rac-1/HIF-1α/DDX3/β-catenin signalling via a tumor suppressor prostate apoptosis response-4 (Par-4) in renal cell carcinoma.Scientific reports · 2023Article
- 3D Tumor Models in Urology.International journal of molecular sciences · 2023Review
- Network-informed discovery of multidrug combinations for ERα+/HER2-/PI3Kα-mutant breast cancer.Cellular and molecular life sciences : CMLS · 2023Article
- Synergic Effect of Metformin and Everolimus on Mitochondrial Dynamics of Renal Cell Carcinoma.Genes · 2022Article
- Multidrug Resistance (MDR): A Widespread Phenomenon in Pharmacological Therapies.Molecules (Basel, Switzerland) · 2022Review
- Advances in Renal Cell Carcinoma Drug Resistance Models.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Repurposed drugs have been evaluated for the management of clear cell renal cell carcinoma (ccRCC), but only a few have influenced the overall survival of patients with advanced disease. To combine repurposed non-oncology with oncological drugs, we applied our validated phenotypic method, which consisted of a reduced experimental part and data modeling. A synergistic optimized multidrug combination (ODC) was identified to significantly reduce the energy levels in cancer remaining inactive in non-cancerous cells. The ODC consisted of Rapta-C, erlotinib, metformin and parthenolide and low doses. Molecular and functional analysis of ODC revealed a loss of adhesiveness and induction of apoptosis. Gene-expression network analysis displayed significant alterations in the cellular metabolism, confirmed by LC-MS based metabolomic analysis, highlighting significant changes in the lipid classes. We used heterotypic in vitro 3D co-cultures and ex vivo organoids to validate the activity of the ODC, maintaining an efficacy of over 70%. Our results show that repurposed drugs can be combined to target cancer cells selectively with prominent activity. The strong impact on cell adherence and metabolism indicates a favorable mechanism of action of the ODC to treat ccRCC.
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Registered trials
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