The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Measurement of PIP3 Levels Reveals an Unexpected Role for p110β in Early Adaptive Responses to p110α-Specific Inhibitors in Luminal Breast Cancer
Open accessAbstract
SUMMARY BYL719, which selectively inhibits the alpha isoform of the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (p110α), is currently in clinical trials for the treatment of solid tumors, especially luminal breast cancers with PIK3CA mutations and/or HER2 amplification. This study reveals that, even among these sensitive cancers, the initial efficacy of p110α inhibition is mitigated by rapid re-accumulation of the PI3K product PIP3 produced by the p110β isoform. Importantly, the reactivation of PI3K mediated by p110β does not invariably restore AKT phosphorylation, demonstrating the limitations of using phospho-AKT as a surrogate to measure PI3K activation. Consistently, we show that the addition of the p110β inhibitor to BYL719 prevents the PIP3 rebound and induces greater antitumor efficacy in HER2-amplified and PIK3CA mutant cancers.
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Cites
Targeting PI3K signalling in cancer: opportunities, challenges and limitations
Engelman, J. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2664 · Cited by 2,445
Self-citationERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics
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“ERBB3 is a receptor that heterodimerizes with HER2 and drives PI3K activation in HER2 -amplified breast cancer cells (Arteaga and Engelman, 2014).”
Self-citationAKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity
Chandarlapaty, S., Sawai, A., Scaltriti, M., Rodrik-Outmezguine, V., Grbovic-Huezo, O., Serra, V., Majumder, P. K., Baselga, J., & Rosen, N. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.10.031 · Cited by 967
Critical role for the p110α phosphoinositide-3-OH kinase in growth and metabolic regulation
Foukas, L. C., Claret, M., Pearce, W., Okkenhaug, K., Meek, S., Peskett, E., Sancho, S., Smith, A. J. H., Withers, D. J., & Vanhaesebroeck, B. (2006) · Nature · doi:10.1038/nature04694 · Cited by 463 · cited 2×
“Among all class IA members, p110a is the isoform predominantly mutated in cancers (Samuels et al., 2004) and has a prominent role in controlling cell growth in solid malignancies (Bader et al., 2006; Foukas et al., 2006; Zhao et al., 2006).”
BackgroundPark, W. S., Do Heo, W., Whalen, J. H., O'Rourke, N. A., Bryan, H. M., Meyer, T., & Teruel, M. N. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.04.008 · Cited by 167
Cited by
The PI3K Pathway in Human Disease
Fruman, D. A., Chiu, H., Hopkins, B. D., Bagrodia, S., Cantley, L. C., & Abraham, R. T. (2017) · Cell · doi:10.1016/j.cell.2017.07.029 · Cited by 2,749
PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer
Glaviano, A., Foo, A. S. C., Lam, H. Y., Yap, K. C. H., Jacot, W., Jones, R. H., Eng, H., Nair, M. G., Makvandi, P., Geoerger, B., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01827-6 · Cited by 2,138
FDA-approved small-molecule kinase inhibitors
Wu, P., Nielsen, T. E., & Clausen, M. H. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.04.005 · Cited by 1,013
Inhibition of the PI3K/AKT/mTOR Pathway in Solid Tumors
LoRusso, P. M. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.0018 · Cited by 470
Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer
Labrie, M., Brugge, J. S., Mills, G. B., & Zervantonakis, I. K. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-022-00454-5 · Cited by 369
Metadata
- Authors
- Costa, C., Ebi, H., Martini, M., Beausoleil, S. A., Faber, A. C., Jakubik, C. T., Huang, A., Wang, Y., Nishtala, M., Hall, B., Rikova, K., Zhao, J., Hirsch, E., Benes, C. H., & Engelman, J. A.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 27
- Issue
- 1
- Pages
- 97-108
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2156918228
- Cited by
- 203
- References
- 5
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Costa, C., Ebi, H., Martini, M., Beausoleil, S. A., Faber, A. C., Jakubik, C. T., Huang, A., Wang, Y., Nishtala, M., Hall, B., Rikova, K., Zhao, J., Hirsch, E., Benes, C. H., & Engelman, J. A. (2015). Measurement of PIP3 Levels Reveals an Unexpected Role for p110β in Early Adaptive Responses to p110α-Specific Inhibitors in Luminal Breast Cancer. Cancer Cell. https://doi.org/10.1016/j.ccell.2014.11.007
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