@article {1118476,
	title = {The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation},
	journal = {Sci Transl Med},
	volume = {9},
	number = {391},
	year = {2017},
	month = {2017 May 24},
	abstract = {Although targeted therapies are often effective systemically, they fail to adequately control brain metastases. In preclinical models of breast cancer that faithfully recapitulate the disparate clinical responses in these microenvironments, we observed that brain metastases evade phosphatidylinositide 3-kinase (PI3K) inhibition despite drug accumulation in the brain lesions. In comparison to extracranial disease, we observed increased HER3 expression and phosphorylation in brain lesions. HER3 blockade overcame the resistance of HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases to PI3K inhibitors, resulting in marked tumor growth delay and improvement in mouse survival. These data provide a mechanistic basis for therapeutic resistance in the brain microenvironment and identify translatable treatment strategies for HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases.},
	issn = {1946-6242},
	doi = {10.1126/scitranslmed.aal4682},
	url = {http://stm.sciencemag.org/content/9/391/eaal4682.short},
	author = {Kodack, David P and Askoxylakis, Vasileios and Ferraro, Gino B and Sheng, Qing and Badeaux, Mark and Goel, Shom and Qi, Xiaolong and Shankaraiah, Ram and Cao, Z Alexander and Ramjiawan, Rakesh R and Bezwada, Divya and Patel, Bhushankumar and Song, Yongchul and Costa, Carlotta and Naxerova, Kamila and Wong, Christina S F and Kloepper, Jonas and Das, Rita and Tam, Angela and Tanboon, Jantima and Duda, Dan G and Miller, C Ryan and Siegel, Marni B and Anders, Carey K and Sanders, Melinda and Estrada, Monica V and Schlegel, Robert and Arteaga, Carlos L and Brachtel, Elena and Huang, Alan and Fukumura, Dai and Engelman, Jeffrey A and Jain, Rakesh K}
}
