Targeting triple-negative breast cancer by inhibiting cancer stem-like cell (CSC) expansion

3^rd World Congress on Women’s Health & Breast Cancer

October 03-05, 2016 London, UK

Guan Chen

Medical College of Wisconsin, USA

Keynote: J Cancer Sci Ther

Abstract :

Triple negative breast cancer (TNBC) is highly progressive and lacks established targets for therapeutic intervention. p38�³ mitogen-activated protein kinase (MAPK) (gene name: MAPK12) is overexpressed in TNBC but overexpressed p38�³ contributes to TNBC remains unknown. Here, we show that p38�³ activation promotes TNBC development and progression by stimulating cancer stem-like cell (CSC) expansion and may serve as a novel therapeutic target for TNBC. p38�³ silencing in TNBC cells inhibits mammosphere formation and reduces levels of key CSC driversâ�� expression including NANOG, Oct3/4, and Sox2. Moreover, p38�³ MAPK-forced expression alone is sufficient to stimulate CSC expansion and to induce malignant transformation with a phenotype resembling to TNBC in vitro and in vivo. Furthermore, p38�³ depends on its activity to stimulate CSC expansion and breast cancer progression, indicating a therapeutic opportunity by application of its pharmacological inhibitor. Indeed, the non-toxic p38�³ specific pharmacological inhibitor pirfenidone selectively inhibits TNBC growth in vitro and/or in vivo and significantly decreases CSC population. Mechanistically, p38�³ stimulates NANOG expression through AP-1 via interaction with c-Jun. These results together demonstrate that p38�³ drives TNBC development and progression and may be thus a novel therapeutic target by stimulating CSC expansion. Inhibiting p38�³ activity with pirfenidone may be a novel strategy for the treatment of TNBC.

Biography :

Guan Chen completed his PhD from Heidelberg University, Germany and Post-doctoral Training from Dana-Farber Cancer Institute, Harvard University, Boston, USA. He has been a tenured full-Professor of Pharmacology at Medical College of Wisconsin for more than 10 years. He serves as an Editorial Board Member of several international Journals.

Email: gchen@mcw.edu