Editors' ChoiceCancer

PIKing the correct therapeutic combination

Sci. Signal.  21 Apr 2015:
Vol. 8, Issue 373, pp. ec103
DOI: 10.1126/scisignal.aab3638

Mutations in PIK3CA, encoding phosphoinositide 3-kinase (PI3K),are common in estrogen receptor (ER)–positive breast cancers, and drugs that inhibit PI3K are in clinical development. By analyzing both mouse models and human patients’ tumors, Bosch et al. discovered that inhibition of PI3K often stimulates the ER transcriptional activity, which then drives tumor growth. By combining PI3K inhibitors with clinically available drugs that inhibit ER, resistance was prevented and tumor regression was achieved in mouse models.

A. Bosch, Z. Li, A. Bergamaschi, H. Ellis, E. Toska, A. Prat, J. J. Tao, D. E. Spratt, N. T. Viola-Villegas, P. Castel, G. Minuesa, N. Morse, J. Rodón, Y. Ibrahim, J. Cortes, J. Perez-Garcia, P. Galvan, J. Grueso, M. Guzman, J. A. Katzenellenbogen, M. Kharas, J. S. Lewis, M. Dickler, V. Serra, N. Rosen, S. Chandarlapaty, M. Scaltriti, J. Baselga, PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor–positive breast cancer. Sci. Transl. Med. 7, 283ra51 (2015). [Abstract]