Journal article

Synergistic activity of letrozole and sorafenib on breast cancer cells

Mara A Bonelli, Claudia Fumarola, Roberta R Alfieri, Silvia La Monica, Andrea Cavazzoni, Maricla Galetti, Rita Gatti, Silvana Belletti, Adrian L Harris, Stephen B Fox, Dean B Evans, Mitch Dowsett, Lesley-Ann Martin, Alberto Bottini, Daniele Generali, Pier Giorgio Petronini

BREAST CANCER RESEARCH AND TREATMENT | SPRINGER | Published : 2010

Abstract

Estrogens induce breast tumor cell proliferation by directly regulating gene expression via the estrogen receptor (ER) transcriptional activity and by affecting growth factor signaling pathways such as mitogen-activated protein kinase (MAPK) and AKT/mammalian target of rapamycin Complex1 (mTORC1) cascades. In this study we demonstrated the preclinical therapeutic efficacy of combining the aromatase inhibitor letrozole with the multi-kinase inhibitor sorafenib in aromatase-expressing breast cancer cell lines. Treatment with letrozole reduced testosterone-driven cell proliferation, by inhibiting the synthesis of estrogens. Sorafenib inhibited cell proliferation in a concentration-dependent man..

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