Integrating leptin and cAMP signalling pathways in triple-negative breast cancer cells

Abstract

Breast cancer is a major cause of cancer death in women in the world. Triple-negative breast cancers, which accounts for 10-20% of all mammary tumours, are characterised by an aggressive phenotype, are often found in younger women and have been associated with poor prognosis. Obesity increases the risk for triple-negative breast cancer occurrence. Because triple-negative breast cancer patients are unresponsive to current targeted therapies and other treatment options are only partially effective, new pharmacological approaches are warranted. The obesity-linked adipokine, leptin, is a well known mitogen/survival factor in breast cancer cells and several studies have addressed the role of leptin in breast cancer pathogenesis and progression. Surprisingly, recent in vitro studies have shown that leptin enhances the anti-proliferative effects of cAMP elevation in triple-negative breast cancer cells by apoptosis induction. In the current review, we discuss on the role of cAMP as a growth suppressor and of leptin as a growth promoting factor in breast cancer cells and we will focus on the molecular pathways involved in the antiproliferative interaction between leptin and cAMP elevation. The rationale for the possible development of a simple, cheap and innovative approach for therapeutic intervention in triple-negative breast cancer, based on the use of cAMP elevating drugs at lower and tolerable doses, will be also discussed.