ArticleInternational journal of molecular sciences2023
Selective Eradication of Colon Cancer Cells Harboring PI3K and/or MAPK Pathway Mutations in 3D Culture by Combined PI3K/AKT/mTOR Pathway and MEK Inhibition.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- LC-MS/MS-based metabolomics analysis and experimental verification reveal the mechanism of Dahuang Mudan Decoction inhibition with the proliferation of colorectal cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Single-cell landscape of melanoma reveals ETV5-driven C3 ID4Frontiers in immunology · 2026Article
- Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.Cellular and molecular life sciences : CMLS · 2025Review
- A Further Case for Targeting PRMT5 and the ERK1/2 and PI3K Pathways in CRC.International journal of molecular sciences · 2025Article
- Current and Emerging Therapies for Targeting the ERK1/2 & PI3K Pathways in Cancer.International journal of molecular sciences · 2025Review
- Review
- Protein-responsive gut hormone tachykinin directs food choice and impacts lifespan.Nature metabolism · 2025Article
- Targeting protein synthesis pathways in MYC-amplified medulloblastoma.Discover oncology · 2025Review
- Single-cell technology reveals the crosstalk between tumor cells and immune cells: driving immune signal transduction and inflammation-mediated cardiac dysfunction in the tumor microenvironment of colorectal cancer.Frontiers in immunology · 2025Article
- Biomedical applications of organoids derived from the digestive system.Frontiers in cell and developmental biology · 2025Review
- Administration of Spermidine and Eugenol Demonstrates Anti-Tumorigenic Efficacy on Metastatic SW620 and Primary Caco-2 Colorectal Cancer Spheroids.International journal of molecular sciences · 2024Article
- Metabolic Response to Small Molecule Therapy in Colorectal Cancer Tracked with Raman Spectroscopy and Metabolomics.Angewandte Chemie (International ed. in English) · 2024Article
- Challenges in validation of combination treatment strategies for CRC using patient-derived organoids.Journal of experimental & clinical cancer research : CR · 2024Review
- Scorpiones, Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1α Signaling Pathway.Chinese journal of integrative medicine · 2024Article
- Pharmacological inhibition of CDK4/6 impairs diffuse pleural mesothelioma 3D spheroid growth and reduces viability of cisplatin-resistant cells.Frontiers in oncology · 2024Article
- PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer.Molecular cancer · 2023Review
- UBXN2A suppresses the Rictor-mTORC2 signaling pathway, an established tumorigenic pathway in human colorectal cancer.Oncogene · 2023Article
- Development of a reliable method for human triple-negative breast cancer organotypic culture: Improving imaging and genomic studies in 3D cultures.Journal of tissue engineeringArticle
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Colorectal cancer (CRC) is the second deadliest cancer in the world. Besides APC and p53 alterations, the PI3K/AKT/MTOR and MAPK pathway are most commonly mutated in CRC. So far, no treatment options targeting these pathways are available in routine clinics for CRC patients. We systematically analyzed the response of CRC cells to the combination of small molecular inhibitors targeting the PI3K and MAPK pathways. We used CRC cells in 2D, 3D spheroid, collagen gel cultures and freshly isolated organoids for drug response studies. Readout for drug response was spheroid or organoid growth, spheroid outgrowth, metabolic activity, Western blotting and immunofluorescence. We found profound tumor cell destruction under treatment with a combination of Torin 1 (inhibiting mTOR), MK2206 (targeting AKT) and selumetinib (inhibiting MEK) in 3D but not in 2D. Induction of cell death was due to apoptosis. Western blot analysis revealed efficient drug action. Gedatolisib, a dual PI3K/mTOR inhibitor, could replace Torin1/MK2206 with similar efficiency. The presence of PI3K and/or RAS-RAF-MAPK pathway mutations accounted for treatment responsiveness. Here, we identified a novel, efficient therapy, which induced proliferation stop and tumor cell destruction in vitro based on the genetic background. These preclinical findings show promise to further test this combi-treatment in vivo in mice and to potentially develop a mutation specific targeted therapy for CRC patients.
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