Hormone-dependent breast cancer: Targeting autophagy and PI3K overcomes Exemestane-acquired resistance

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Amaral, C (Author) Other; Augusto, TV (Author) Other; Tavares da Silva, E (Author) Other; Roleira, FMF (Author) Other; Georgina Correia da Silva (Author) FFUP; Teixeira, NA (Author) FFUP

Journal

Title: Journal of Steroid Biochemistry and Molecular Biology

Vol. 183

Pages: 51-61

ISSN: 0960-0760

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 16 Citations

Scopus - 13 Citations

Other information

Authenticus ID: P-00P-PE8

DOI: 10.1016/j.jsbmb.2018.05.006

Abstract (EN): The leading cause of cancer death in women around the world is breast cancer. The aromatase inhibitors (AIs) are considered - as first-line treatment for estrogen receptor-positive (ER+) breast tumors, in postmenopausal women. Exemestane (Exe) is a powerful steroidal AI, however, despite its therapeutic success, Exe-acquired resistance may occur leading to tumor relapse. Our group previously demonstrated that autophagy acts as a pro survival process in Exe-induced cell death of ER+ sensitive breast cancer cells. In this work, the role of autophagy and its relationship with the PI3K/AKT/mTOR pathway in Exe-acquired resistance was explored. In that way, the mechanism behind the effects of the combination of Exe with pan-PI3K, or autophagic inhibitors, was studied in a long-term estrogen deprived ER+ breast cancer cell line (LTEDaro cells). Our results indicate that Exe induces autophagy as a cytoprotective mechanism linked to acquired resistance. Moreover, it was demonstrated that by inhibiting autophagy and/or PI3K pathway it is possible to revert Exe-resistance through apoptosis promotion, disruption of cell cycle, and inhibition of cell survival pathways. This work provides new insights into the mechanisms involved in Exe-acquired resistance, pointing autophagy as an attractive therapeutic target to surpass it. Thus, it highlights new targets that together with aromatase inhibition may improve ER+ breast cancer therapy, overcoming AIs-acquired resistance.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11