| First Author | Schwartz S | Year | 2015 |
| Journal | Cancer Cell | Volume | 27 |
| Issue | 1 | Pages | 109-22 |
| PubMed ID | 25544636 | Mgi Jnum | J:218824 |
| Mgi Id | MGI:5618557 | Doi | 10.1016/j.ccell.2014.11.008 |
| Citation | Schwartz S, et al. (2015) Feedback suppression of PI3Kalpha signaling in PTEN-mutated tumors is relieved by selective inhibition of PI3Kbeta. Cancer Cell 27(1):109-22 |
| abstractText | In PTEN-mutated tumors, we show that PI3Kalpha activity is suppressed and PI3K signaling is driven by PI3Kbeta. A selective inhibitor of PI3Kbeta inhibits the Akt/mTOR pathway in these tumors but not in those driven by receptor tyrosine kinases. However, inhibition of PI3Kbeta only transiently inhibits Akt/mTOR signaling because it relieves feedback inhibition of IGF1R and other receptors and thus causes activation of PI3Kalpha and a rebound in downstream signaling. This rebound is suppressed and tumor growth inhibition enhanced with combined inhibition of PI3Kalpha and PI3Kbeta. 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. |
