Leptin-Signaling Pathways as Therapeutic Targets in Cancer

Abstract

Evidences from molecular, clinical, and epidemiological studies have shown that high plasma level of leptin correlate with obese state and is emerging as a key adipocytokine mediating the molecular effects of obesity on cancer. Dysregulation of leptin influences various stages of carcinogenesis from initiation and growth to metastatic progression. In addition to activating its canonical signaling, leptin is now known to functionally interact with multiple oncogenic pathways. This ``hyperactive leptin-signaling network{''} in cancer cells leads to simultaneous activation of multiple oncogenic pathways leading to increased proliferation, decreased apoptosis, acquisition of mesenchymal phenotype, and enhanced migration and invasion potential of tumor cells. Leptin is also known to interact with other important molecular effectors such as estrogen, IGF-1, insulin, VEGF, and inflammatory cytokines and achieve a wider impact across various tumor types. Development of a better understanding of leptin-signaling network has provided multiple therapeutic opportunities to inhibit important nodes of this network. This article presents an overview of the studies investigating the involvement of leptin and hyperactive leptin-signaling network in cancer progression and strategies to inhibit leptin signaling in cancer.