Inhibition of formyl peptide receptor 1 reduces the efficacy of anticancer chemotherapy against carcinogen-induced breast cancer.

Abstract

The loss-of-function mutation of formyl peptide receptor 1 (FPR1) has a negative impact on the progression-free and overall survival of breast cancer patients treated with anthracycline-based adjuvant chemotherapy. This effect may be attributed to the fact that chemotherapy-induced antitumor immunity requires FPR1 and that such anticancer immune responses are responsible for the long-term effects of chemotherapy. Here, we investigated the possible contribution of FPR1 to the efficacy of a combination of mitoxantrone (MTX) and cyclophosphamide (CTX) for the treatment of hormone-induced breast cancer. Breast cancer induced by a combination of medroxyprogesterone acetate (MPA) and 7,12-Dimethylbenz[a]anthracene (DMBA) could be successfully treated with MTX plus CTX in thus far that tumor growth was retarded and overall survival was extended (as compared to vehicle-only treated controls). However, the therapeutic efficacy of the combination therapy was completely abolished when FPR1 receptors were blocked by means of cyclosporin H (CsH). Future genetic studies on neoadjuvant chemotherapy-treated breast cancers are warranted to validate these findings at the clinical level.

• Authors: Elisa E Baracco, Federico Pietrocola, Aitziber Buqué, Norma Bloy, Laura Senovilla, Laurence Zitvogel, Erika Vacchelli, Guido Kroemer
• Journal: Oncoimmunology (Oncoimmunology) Vol. 5 Issue 6 Pg. e1139275 (Jun 2016) ISSN: 2162-4011 [Print] United States
• PMID: 27471610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)