ArticleMolecular oncology2020
Optimized low-dose combinatorial drug treatment boosts selectivity and efficacy of colorectal carcinoma treatment.
Article in Molecular oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
19 citing papers in PubMed, 29 citations in OpenAlex.
- Phase II Trial of Vemurafenib and Sorafenib Combination in AdvancedJournal of immunotherapy and precision oncology · 2026Article
- Combined Treatment of Sodium Butyrate and Bromelain Enhanced Anticancer Effects in Colorectal Cancer Cell Lines: A Promising Therapeutic Approach.International journal of molecular sciences · 2025Article
- Rational Design of Non-Toxic Multidrug Combinations Demonstrates Durable and Hypoxia-Enhanced Efficacy Against Renal Cell Carcinoma.Pharmaceutics · 2025Article
- Challenges in validation of combination treatment strategies for CRC using patient-derived organoids.Journal of experimental & clinical cancer research : CR · 2024Review
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- Camptothesome-based combination nanotherapeutic regimen for improved colorectal cancer immunochemotherapy.Biomaterials · 2024Article
- New Therapeutic Perspectives in Prostate Cancer: Patient-Derived Organoids and Patient-Derived Xenograft Models in Precision Medicine.Biomedicines · 2023Review
- Titin as a potential novel therapeutic target in colorectal cancer.Journal of cellular and molecular medicine · 2023Article
- 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
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- Identifying mutant-specific multi-drug combinations using comparative network reconstruction.iScience · 2022Article
- 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
- Forcing dividing cancer cells to die; low-dose drug combinations to prevent spindle pole clustering.Apoptosis : an international journal on programmed cell death · 2021Review
- Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets.Cancers · 2021Article
- Opportunities and Challenges in Tunneling Nanotubes Research: How Far from Clinical Application?International journal of molecular sciences · 2021Review
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Corrections and comments
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Authors and funding
23 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The current standard of care for colorectal cancer (CRC) is a combination of chemotherapeutics, often supplemented with targeted biological drugs. An urgent need exists for improved drug efficacy and minimized side effects, especially at late-stage disease. We employed the phenotypically driven therapeutically guided multidrug optimization (TGMO) technology to identify optimized drug combinations (ODCs) in CRC. We identified low-dose synergistic and selective ODCs for a panel of six human CRC cell lines also active in heterotypic 3D co-culture models. Transcriptome sequencing and phosphoproteome analyses showed that the mechanisms of action of these ODCs converged toward MAP kinase signaling and cell cycle inhibition. Two cell-specific ODCs were translated to in vivo mouse models. The ODCs reduced tumor growth by ~80%, outperforming standard chemotherapy (FOLFOX). No toxicity was observed for the ODCs, while significant side effects were induced in the group treated with FOLFOX therapy. Identified ODCs demonstrated significantly enhanced bioavailability of the individual components. Finally, ODCs were also active in primary cells from CRC patient tumor tissues. Taken together, we show that the TGMO technology efficiently identifies selective and potent low-dose drug combinations, optimized regardless of tumor mutation status, outperforming conventional chemotherapy.
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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 OpenQuestion graph.