ESTRO Multidisciplinary Management of Breast Cancer 2017

The PI3K Pathway is Activated in Breast Cancer

Growth factor receptor

Estrogen

PI3K/mTOR pathway activation is a hallmark of HR+/HER2– breast cancer cells that have developed resistance to endocrine therapy 1,2

The ER pathway is upregulated in tumors from patients treated with PI3K inhibitors 1

Buparlisib Pan-PI3K inhibitor

PI3K

ER

Dual blockade of the PI3K/mTOR and ER pathways may therefore restore sensitivity to endocrine therapy 1,3,4

Fulvestrant

mTORC2

AKT

Protein synthesis

mTORC1

Tumor growth and progression Resistance to endocrine therapy

ER, estrogen receptor; HER2–, human epidermal growth factor receptor 2 negative; HR+, hormone receptor-positive; mTOR, mammalian target of rapamycin; mTORC, mammalian target of rapamycin complex; PI3K, phosphatidylinositol 3-kinase. 1. Bosch A, et al. Sci Transl Med. 2015;7:283ra51; 2. Miller TW, et al. Cancer Discov. 2011;1:338–351; 3. Fox EM, e t al. Front Oncol . 2012;2:145; 4. Yardley D, et al. Adv Ther. 2013;30:870–884.