"Overcoming breast cancer drug resistance with mTOR inhibitors". Could it be a myth or a real possibility in the short-term future?

Nadia Margariti (1) , Stephen B. Fox (2) , Alberto Bottini (3) , Daniele Generali (1, 3)

1 Centro di Medicina Molecolare
2 Department of Pathology
3 Unità di Patologia Mammaria, Senologia e Breast Unit, Centro di Medicina Molecolare

The mTOR pathway is pivotal not only in tumorigenesis but also in chemotherapy and hormonal drug sensitivity. It is clear that improvements in using new targeted therapies are required to improve breast cancer (BC) outcome. Nevertheless, to achieve this, new molecular biomarkers are required to define the potential sensitivity or resistance of cancer cells. By targeting the mTOR pathway, several critical central transduction pathways that sustain BC are abrogated (HER-2/Neu and the estrogen receptor pathway). Thus, the compounds that inhibit mTOR have a double mechanism of toxicity on BC cells when used in combination with a currently used drug: (1) overcoming primary drug resistance and (2) restoring sensitivity when resistance arises after long-term exposure. This review covers the utility of inhibitors of the mTOR pathway in BC and emphasizes the new paradigm of close symbiosis between oncology and molecular biology to better profiling and treating BC with a targeted approach. In particular, we focused on the new drug RAD001 (Everolimus) due to the great results from preclinical and clinical trials make it the most hopeful compound among mTOR inhibitors for the treatment of BC.

Mots clés: mTOR pathway; Temsirolimus; Everolimus; Breast cancer; Drug resistance; Aromatase inhibitor

Nadia Margariti, Stephen B. Fox, Alberto Bottini, Daniele Generali. "Overcoming breast cancer drug resistance with mTOR inhibitors". Could it be a myth or a real possibility in the short-term future?. Breast Cancer Research and Treatment, 2010, 128 (3), pp.599-606. ⟨10.1007/s10549-010-0986-9⟩. ⟨hal-00615397⟩