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المؤلفون: Brigitta G. Baumert, Erik P. Sulman, Jan Koster, Rogier Dik, Yoran Broersma, Tonny Lagerweij, Rogier Versteeg, Lucas J A Stalpers, D. P. Noske, Irene Roelofs, Jhon Alexander Marin Soto, Sjors G J G In 't Veld, Peter Sminia, Naomi Petersen, Louis Vermeulen, Maria C. Lecca, Eelke Brands, Ravi S. Narayan, Bakhos A. Tannous, Renée X. de Menezes, David Bailey, Jian Teng, Bart A Westerman, Ben J. Slotman, Thomas Wurdinger, Piet Molenaar, Fleur M G Cornelissen, Roel G.W. Verhaak, Colin Watts, Frederick F. Lang, Kristiaan J. Lenos, Wessel N. van Wieringen, Philip van Kuiken
المساهمون: Oncogenomics, CCA - Cancer biology and immunology, Tytgat Institute for Liver and Intestinal Research, Center of Experimental and Molecular Medicine, Radiotherapy, AGEM - Re-generation and cancer of the digestive system, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Methodology, Radiation Oncology, Neurosurgery, Epidemiology and Data Science, Molecular cell biology and Immunology, Internal medicine
المصدر: Nature Communications
Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020)
Nature communications, 11(1):2935. Nature Publishing Group
Nature Communications, 11(1):2935
Narayan, R S, Molenaar, P, Teng, J, Cornelissen, F M G, Roelofs, I, Menezes, R, Dik, R, Lagerweij, T, Broersma, Y, Petersen, N, Marin Soto, J A, Brands, E, van Kuiken, P, Lecca, M C, Lenos, K J, Int Veld, S G J G, van Wieringen, W, Lang, F F, Sulman, E, Verhaak, R, Baumert, B G, Stalpers, L J A, Vermeulen, L, Watts, C, Bailey, D, Slotman, B J, Versteeg, R, Noske, D, Sminia, P, Tannous, B A, Wurdinger, T, Koster, J & Westerman, B A 2020, ' A cancer drug atlas enables synergistic targeting of independent drug vulnerabilities ', Nature Communications, vol. 11, no. 1, 2935 . https://doi.org/10.1038/s41467-020-16735-2, https://doi.org/10.1038/s41467-020-16735-2مصطلحات موضوعية: 0301 basic medicine, Drug, Cancer therapy, Computer science, Cell Survival, Science, media_common.quotation_subject, Cancer drugs, General Physics and Astronomy, Antineoplastic Agents, Breast Neoplasms, Computational biology, General Biochemistry, Genetics and Molecular Biology, Drug synergism, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Cell Line, Tumor, medicine, Animals, Humans, lcsh:Science, Cancer genetics, Melanoma, media_common, Multidisciplinary, Computational Biology, Drug Synergism, General Chemistry, medicine.disease, Computational biology and bioinformatics, Drug Combinations, 030104 developmental biology, Logistic Models, Drug screening, 030220 oncology & carcinogenesis, Pharmacogenomics, lcsh:Q, Glioblastoma
الوصف: Personalized cancer treatments using combinations of drugs with a synergistic effect is attractive but proves to be highly challenging. Here we present an approach to uncover the efficacy of drug combinations based on the analysis of mono-drug effects. For this we used dose-response data from pharmacogenomic encyclopedias and represent these as a drug atlas. The drug atlas represents the relations between drug effects and allows to identify independent processes for which the tumor might be particularly vulnerable when attacked by two drugs. Our approach enables the prediction of combination-therapy which can be linked to tumor-driving mutations. By using this strategy, we can uncover potential effective drug combinations on a pan-cancer scale. Predicted synergies are provided and have been validated in glioblastoma, breast cancer, melanoma and leukemia mouse-models, resulting in therapeutic synergy in 75% of the tested models. This indicates that we can accurately predict effective drug combinations with translational value.
Drug synergies impact the efficacy of combination therapies but are difficult to identify. Here Narayan et al. describe the drug atlas, a method to predict effective drug combinations from common exclusive drug effects providing a resource for exploring and understanding effective drug combinations.
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