ArticleCancers2020
Optimized Combination of HDACI and TKI Efficiently Inhibits Metabolic Activity in Renal Cell Carcinoma and Overcomes Sunitinib Resistance.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- APOC2 Promotes Clear Cell Renal Cell Carcinoma Progression via Activation of the JAK-STAT Signaling Pathway.Current issues in molecular biology · 2025Article
- Getting the right combination to break the epigenetic code.Nature reviews. Clinical oncology · 2025Review
- Von Hippel-Lindau protein signalling in clear cell renal cell carcinoma.Nature reviews. Urology · 2024Review
- HDAC8 Enhances the Function of HIF-2α by Deacetylating ETS1 to Decrease the Sensitivity of TKIs in ccRCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Proteomics analysis of histone deacetylase inhibitor-resistant solid tumors reveals resistant signatures and potential drug combinations.Acta pharmacologica Sinica · 2024Article
- Platform combining statistical modeling and patient-derived organoids to facilitate personalized treatment of colorectal carcinoma.Journal of experimental & clinical cancer research : CR · 2023Article
- Network-informed discovery of multidrug combinations for ERα+/HER2-/PI3Kα-mutant breast cancer.Cellular and molecular life sciences : CMLS · 2023Article
- Identification of novel and potent dual-targeting HDAC1/SPOP inhibitors using structure-based virtual screening, molecular dynamics simulation and evaluation ofFrontiers in pharmacology · 2023Article
- Molecular mechanisms of resistance to tyrosine kinase inhibitor in clear cell renal cell carcinoma.International journal of urology : official journal of the Japanese Urological Association · 2022Review
- Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma.Frontiers in pharmacology · 2022Article
- Advances in Renal Cell Carcinoma Drug Resistance Models.Frontiers in oncology · 2022Review
- Drug Repurposing to Identify a Synergistic High-Order Drug Combination to Treat Sunitinib-Resistant Renal Cell Carcinoma.Cancers · 2021Article
- Molecular and Functional Analysis of Sunitinib-Resistance Induction in Human Renal Cell Carcinoma Cells.International journal of molecular sciences · 2021Article
- Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets.Cancers · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Clear cell renal cell carcinoma (ccRCC) is characterized by high histone deacetylase (HDAC) activity triggering both cell motility and the development of metastasis. Therefore, there is an unmet need to establish innovative strategies to advance the use of HDAC inhibitors (HDACIs). We selected a set of tyrosine kinase inhibitors (TKIs) and HDACIs to test them in combination, using the validated therapeutically guided multidrug optimization (TGMO) technique based on experimental testing and in silico data modeling. We determined a synergistic low-dose three-drug combination decreasing the cell metabolic activity in metastatic ccRCC cells, Caki-1, by over 80%. This drug combination induced apoptosis and showed anti-angiogenic activity, both in original Caki-1 and in sunitinib-resistant Caki-1 cells. Through phosphoproteomic analysis, we revealed additional targets to improve the translation of this combination in 3-D (co-)culture systems. Cell-cell and cell-environment interactions increased, reverting the invasive and metastatic phenotype of Caki-1 cells. Our data suggest that our optimized low-dose drug combination is highly effective in complex in vitro settings and promotes the activity of HDACIs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.