Oncogenic role and therapeutic target of leptin signaling in colorectal cancer

Expert Opin Ther Targets. 2014 Aug;18(8):961-71. doi: 10.1517/14728222.2014.926889. Epub 2014 Jun 19.

Abstract

Introduction: Obesity is characterized by high secretion of several cytokines from adipose tissue and is a recognized risk factor for many cancers. Among these cytokines, leptin mainly produced by adipose tissue and cancer cells is the most studied adipokine. Leptin is an activator of cell proliferation, an antiapoptotic molecule and inducer of cancer stem cells in many cell types, and its critical roles in obesity-related tumorigenesis are based on its oncogenic, mitogenic, pro-inflammatory and pro-angiogenic actions.

Areas covered: These leptin-induced signals and action are critical for their biological effects on energy balance, adiposity, endocrine systems, immunity, angiogenesis as well as oncogenesis. This review focuses on the up-to-date knowledge on the oncogenic role of leptin signaling, clinical significance and specific drug target development in colorectal cancer (CRC). Additionally, leptin-induced angiogenic ability and molecular mechanisms in CRC cells are discussed.

Expert opinion: Stringent binding affinity of leptin/Ob-R and overexpression of leptin/Ob-R and their targets in cancer cells make it a unique drug target for prevention and treatment of CRC, particularly in obesity colorectal patients.

Keywords: colorectal cancer; leptin; leptin antagonist; leptin signaling; tumor angiogenesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / pathology
  • Drug Design
  • Humans
  • Leptin / metabolism*
  • Molecular Targeted Therapy
  • Obesity / complications
  • Risk Factors
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Leptin