The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Feedback Suppression of PI3Kα Signaling in PTEN-Mutated Tumors Is Relieved by Selective Inhibition of PI3Kβ
Open accessAbstract
SUMMARY In PTEN-mutated tumors, we show that PI3Kα activity is suppressed and PI3K signaling is driven by PI3Kβ. A selective inhibitor of PI3Kβ inhibits the Akt/mTOR pathway in these tumors but not in those driven by receptor tyrosine kinases. However, inhibition of PI3Kβ only transiently inhibits Akt/mTOR signaling because it relieves feedback inhibition of IGF1R and other receptors and thus causes activation of PI3Kα and a rebound in downstream signaling. This rebound is suppressed and tumor growth inhibition enhanced with combined inhibition of PI3Kα and PI3Kβ. In PTEN deficient models of prostate cancer, this effective inhibition of PI3K causes marked activation of androgen receptor activity. Combined inhibition of both PI3K isoforms and androgen receptor results in major tumor regressions.
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Cites
Comprehensive molecular portraits of human breast tumours
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11412 · Cited by 12,129
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
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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
Self-citationToledo, L. I., Murga, M., Zur, R., Soria, R., Rodriguez, A., Martinez, S., Oyarzabal, J., Pastor, J., Bischoff, J. R., & Fernandez-Capetillo, O. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2076 · Cited by 465
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
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Integrative Clinical Genomics of Advanced Prostate Cancer
Robinson, D., Van Allen, E. M., Wu, Y.-M., Schultz, N., Lonigro, R. J., Mosquera, J.-M., Montgomery, B., Taplin, M.-E., Pritchard, C. C., Attard, G., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.001 · Cited by 3,645
Self-citationThe 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
Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer
Watson, P. A., Arora, V. K., & Sawyers, C. L. (2015) · Nature Reviews Cancer · doi:10.1038/nrc4016 · Cited by 1,536
Self-citationFDA-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
The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling
Shorning, B. Y., Dass, M. S., Smalley, M. J., & Pearson, H. B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124507 · Cited by 616
Metadata
- Authors
- Schwartz, S., Wongvipat, J., Trigwell, C. B., Hancox, U., Carver, B. S., Rodrik-Outmezguine, V., Will, M., Yellen, P., de Stanchina, E., Baselga, J., Scher, H. I., Barry, S. T., Sawyers, C. L., Chandarlapaty, S., & Rosen, N.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 27
- Issue
- 1
- Pages
- 109-122
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2071463092
- Cited by
- 246
- References
- 7
- FWCI
- 10.22
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Schwartz, S., Wongvipat, J., Trigwell, C. B., Hancox, U., Carver, B. S., Rodrik-Outmezguine, V., Will, M., Yellen, P., de Stanchina, E., Baselga, J., Scher, H. I., Barry, S. T., Sawyers, C. L., Chandarlapaty, S., & Rosen, N. (2015). Feedback Suppression of PI3Kα Signaling in PTEN-Mutated Tumors Is Relieved by Selective Inhibition of PI3Kβ. Cancer Cell. https://doi.org/10.1016/j.ccell.2014.11.008
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