The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
A chemical-genetic screen reveals a mechanism of resistance to PI3K inhibitors in cancer
Open accessAbstract
Linking the molecular aberrations of cancer to drug responses could guide treatment choice and identify new therapeutic applications. However, there has been no systematic approach for analyzing gene-drug interactions in human cells. We establish a multiplexed assay to study the cellular fitness of a panel of engineered isogenic cancer cells in response to a collection of drugs, enabling the systematic analysis of thousands of gene-drug interactions. Applying this approach to breast cancer revealed various synthetic-lethal interactions and drug resistance mechanisms, some of which were known, thereby validating the method. NOTCH pathway activation, which occurs frequently in breast cancer, unexpectedly conferred resistance to PI3K inhibitors, which are currently undergoing clinical trials in breast cancer patients. NOTCH1 and downstream induction of c-MYC overrode the dependency of cells on the PI3K/mTOR pathway for proliferation. These data reveal a novel mechanism of resistance to PI3K inhibitors with direct clinical implications.
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Cites
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers
Fong, P. C., Boss, D. S., Yap, T. A., Tutt, A., Wu, P., Mergui-Roelvink, M., Mortimer, P., Swaisland, H., Lau, A., O'Connor, M. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0900212 · Cited by 3,634
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Tredan, O., Galmarini, C. M., Patel, K., & Tannock, I. F. (2007) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djm135 · Cited by 2,116
Vogel, C. L., Cobleigh, M. A., Tripathy, D., Gutheil, J. C., Harris, L. N., Fehrenbacher, L., Slamon, D. J., Murphy, M., Novotny, W. F., Burchmore, M., et al. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.20.3.719 · Cited by 1,860
Interaction of the Fanconi Anemia Proteins and BRCA1 in a Common Pathway
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Cited by
Dang, C. V. (2012) · Cell · doi:10.1016/j.cell.2012.03.003 · Cited by 3,390
Targeting PI3K in cancer: mechanisms and advances in clinical trials
Yang, J., Nie, J., Ma, X., Wei, Y., Peng, Y., & Wei, X. (2019) · Molecular Cancer · doi:10.1186/s12943-019-0954-x · Cited by 1,520
Recent advances in therapeutic strategies for triple-negative breast cancer
Li, Y., Zhang, H., Merkher, Y., Chen, L., Liu, N., Leonov, S., & Chen, Y. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01341-0 · Cited by 956
The PI3K/AKT/mTOR pathway in breast cancer: targets, trials and biomarkers
Paplomata, E., & O’Regan, R. (2014) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758834014530023 · Cited by 593
Masui, K., Tanaka, K., Akhavan, D., Babic, I., Gini, B., Matsutani, T., Iwanami, A., Liu, F., Villa, G. R., Gu, Y., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.013 · Cited by 407
Metadata
- Authors
- Muellner, M. K., Uras, I. Z., Gapp, B. V., Kerzendorfer, C., Smida, M., Lechtermann, H., Craig-Mueller, N., Colinge, J., Duernberger, G., & Nijman, S. M. B.
- Venue
- Nature Chemical Biology
- Published
- 2011-09-25
- Volume
- 7
- Issue
- 11
- Pages
- 787-793
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2118217667
- Cited by
- 165
- References
- 5
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- green
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- Muellner, M. K., Uras, I. Z., Gapp, B. V., Kerzendorfer, C., Smida, M., Lechtermann, H., Craig-Mueller, N., Colinge, J., Duernberger, G., & Nijman, S. M. B. (2011). A chemical-genetic screen reveals a mechanism of resistance to PI3K inhibitors in cancer. Nature Chemical Biology. https://doi.org/10.1038/nchembio.695
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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