My research group focuses on identifying mechanisms that limit the sensitivity to targeted therapy in solid tumors, in particular to PI3K/Akt/mTOR inhibitors and anti-HER2 agents. By investigating how cancer cells escape the therapeutic pressure of these drugs, we can better identify patients who are more likely to respond to a specific therapy and increase effectiveness of such therapies by testing novel combinations. Concomitantly, we analyze biopsies obtained from patients who were treated with the same compounds as the ones we study in the laboratory. This is necessary in order to validate our preclinical findings and to uncover new (and targetable) possible genomic aberrations acquired by cancer cells during therapeutic stress and selection. Our final aim is to provide insights into designing more-effective clinical trials that test novel therapeutic combinations in precise subsets of cancer patient populations.

Publications

Elkabets M, Vora S, Juric D, Morse N, Mino-Kenudson M, Muranen T, Tao J, Campos AB, Rodon J, Ibrahim YH, Serra V, Rodrik-Outmezguine V, Hazra S, Singh S, Kim P, Quadt C, Liu M, Huang A, Rosen N, Engelman JA, Scaltriti M, Baselga J. mTORC1 inhibition is required for sensitivity to PI3K p110α inhibitors in PIK3CA-mutant breast cancer. Sci Transl Med. 2013 Jul 31;5(196):196ra99. doi: 10.1126/scitranslmed.3005747.

Serra V, Eichhorn PJ, García-García C, Ibrahim YH, Prudkin L, Sánchez G, Rodríguez O, Antón P, Parra JL, Marlow S, Scaltriti M, Pérez-Garcia J, Prat A, Arribas J, Hahn WC, Kim SY, Baselga J. K3/4 mediate resistance to PI3K pathway inhibitors in breast cancer. J Clin Invest. 2013 Jun 3;123(6):2551-63. doi: 10.1172/JCI66343. Epub 2013 May 1.

Ibrahim YH, García-García C, Serra V, He L, Torres-Lockhart K, Prat A, Anton P, Cozar P, Guzmán M, Grueso J, Rodríguez O, Calvo MT, Aura C, Díez O, Rubio IT, Pérez J, Rodón J, Cortés J, Ellisen LW, Scaltriti M, Baselga J. PI3K inhibition impairs BRCA1/2 expression and sensitizes BRCA-proficient triple-negative breast cancer to PARP inhibition. Cancer Discov. 2012 Nov;2(11):1036-47. doi: 10.1158/2159-8290.CD-11-0348. Epub 2012 Aug 22.

Scaltriti M, Eichhorn PJ, Cortés J, Prudkin L, Aura C, Jiménez J, Chandarlapaty S, Serra V, Prat A, Ibrahim YH, Guzmán M, Gili M, Rodríguez O, Rodríguez S, Pérez J, Green SR, Mai S, Rosen N, Hudis C, Baselga J. Cyclin E amplification/overexpression is a mechanism of trastuzumab resistance in HER2+ breast cancer patients. Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3761-6. doi: 10.1073/pnas.1014835108. Epub 2011 Feb 14.

Scaltriti M, Rojo F, Ocaña A, Anido J, Guzman M, Cortes J, Di Cosimo S, Matias-Guiu X, Ramon y Cajal S, Arribas J, Baselga J. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst. 2007 Apr 18;99(8):628-38.