bioRxiv preprint doi: https://doi.org/10.1101/700625; this version posted July 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Combined inhibition of mTOR and PIKKs exploits replicative and checkpoint vulnerabilities to induce death of PI3K-activated triple-negative breast cancer cells Sameer S. Chopra,1,3,5 Anne Jenney,1,3 Adam Palmer,1,3 Mario Niepel,1,3 Mirra Chung,1,3 Caitlin Mills,1,3 Sindhu Carmen Sivakumaren,2,5 Qingsong Liu,2,5 Jia-Yun Chen,1 Clarence Yapp,1,3 John M. Asara,4 Nathanael S. Gray,2,5 Peter K. Sorger1,3* 1Laboratory of Systems Pharmacology, 2Dept. of Biological Chemistry and Molecular Pharmacology, 3Harvard Ludwig Center, 4Division of Signal Transduction, Beth Israel Deaconess Medical Center, 5Dana-Farber Cancer Institute Harvard Medical School, 200 Longwood Avenue, Boston, MA 02215 *Corresponding:
[email protected] Page 1 bioRxiv preprint doi: https://doi.org/10.1101/700625; this version posted July 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. SUMMARY Frequent mutation of genes in the PI3K/AKT/mTOR signaling pathway in human cancers has stimulated large investments in therapeutic drugs but clinical successes have been rare.