ESTRO Multidisciplinary Management of Breast Cancer 2017

The PI3K Pathway is Activated in

Breast Cancer

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

Dual blockade of the PI3K/mTOR and ER pathways may therefore restore

sensitivity to endocrine therapy

1,3,4

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.

Growth factor receptor

Protein

synthesis

AKT

mTORC2

PI3K

Buparlisib

Pan-PI3K inhibitor

Tumor growth and progression

Resistance to endocrine therapy

Fulvestrant

Estrogen

mTORC1