The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation
David P. Kodack(Massachusetts General Hospital), Vasileios Askoxylakis(Massachusetts General Hospital), Gino B. Ferraro(Massachusetts General Hospital), Qing Sheng(Novartis (Switzerland)), Mark Badeaux(Massachusetts General Hospital), Shom Goel(Massachusetts General Hospital), Xiaolong Qi(Massachusetts General Hospital), Ram C. Shankaraiah(Massachusetts General Hospital), Zheng Cao(Novartis (Switzerland)), Rakesh R. Ramjiawan(Massachusetts General Hospital), Divya Bezwada(Massachusetts General Hospital), Bhushankumar Patel(Massachusetts General Hospital), Yongchul Song(Center for Cancer Research), Carlotta Costa(Center for Cancer Research), Kamila Naxerova(Massachusetts General Hospital), Christina S.F. Wong(Massachusetts General Hospital), Jonas Kloepper(Massachusetts General Hospital), Rita Das(Novartis (Switzerland)), Angela Tam(Novartis (Switzerland)), Jantima Tanboon(MGH Institute of Health Professions), Dan G. Duda(Massachusetts General Hospital), C. Ryan Miller(University of North Carolina at Chapel Hill), Marni B. Siegel(University of North Carolina at Chapel Hill), Carey K. Anders(University of North Carolina at Chapel Hill), Melinda E. Sanders(Vanderbilt University), Mónica V. Estrada(Breast Cancer Research Foundation), Robert Schlegel(Novartis (Switzerland)), Carlos L. Arteaga(Vanderbilt University), Elena F. Brachtel(MGH Institute of Health Professions), Alan Huang(Novartis (Switzerland)), Dai Fukumura(Massachusetts General Hospital), Jeffrey A. Engelman(Center for Cancer Research), Rakesh K. Jain(Massachusetts General Hospital)
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Abstract
The brain microenvironment triggers HER3-dependent de novo resistance to therapies targeting PI3K or HER2 in HER2-positive and/or PIK3CA -mutant breast cancer cells.
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