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Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Apr 10, 2017; 8(2): 106-119
Published online Apr 10, 2017. doi: 10.5306/wjco.v8.i2.106
Leptin signaling and cancer chemoresistance: Perspectives
Pierre V Candelaria, Antonio Rampoldi, Adriana Harbuzariu, Ruben R Gonzalez-Perez
Pierre V Candelaria, Antonio Rampoldi, Adriana Harbuzariu, Ruben R Gonzalez-Perez, Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, United States
Author contributions: Candelaria PV, Rampoldi A and Harbuzariu A have been involved equally, researched the literature, wrote the paper and have read and approved the final manuscript; Gonzalez-Perez RR researched the literature, analyzed data, wrote and edited the paper.
Supported by Department of Defense (DOD), Congressionally Direct Medical Research Program (CDMRP), No. W81XWH- 13-1-0382; National Institute of Health (NIH)/National Cancer Institute (NCI), No. 1R41CA183399-01A; Pilot Project Award from MSM (Morehouse School of Medicine)/Tuskegee University/University of Alabama in Birmingham (UAB) Cancer Center partnership, No. 5U54CA118638; and the National Institute on Minority Health and Health Disparities (NIMHD) of NIH, No. 5S21MD00101.
Conflict-of-interest statement: The authors declare no potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ruben R Gonzalez-Perez, PhD, Professor, Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Drive SW, Hugh Gloster Bldg., Room 329, Atlanta, GA 30310, United States. rgonzalez@msm.edu
Telephone: +1-404-7521581 Fax: +1-404-7521179
Received: September 29, 2016
Peer-review started: October 7, 2016
First decision: December 1, 2016
Revised: December 20, 2016
Accepted: February 28, 2017
Article in press: February 28, 2017
Published online: April 10, 2017
Abstract

Obesity is a major health problem and currently is endemic around the world. Obesity is a risk factor for several different types of cancer, significantly promoting cancer incidence, progression, poor prognosis and resistance to anti-cancer therapies. The study of this resistance is critical as development of chemoresistance is a serious drawback for the successful and effective drug-based treatments of cancer. There is increasing evidence that augmented adiposity can impact on chemotherapeutic treatment of cancer and the development of resistance to these treatments, particularly through one of its signature mediators, the adipokine leptin. Leptin is a pro-inflammatory, pro-angiogenic and pro-tumorigenic adipokine that has been implicated in many cancers promoting processes such as angiogenesis, metastasis, tumorigenesis and survival/resistance to apoptosis. Several possible mechanisms that could potentially be developed by cancer cells to elicit drug resistance have been suggested in the literature. Here, we summarize and discuss the current state of the literature on the role of obesity and leptin on chemoresistance, particularly as it relates to breast and pancreatic cancers. We focus on the role of leptin and its significance in possibly driving these proposed chemoresistance mechanisms, and examine its effects on cancer cell survival signals and expansion of the cancer stem cell sub-populations.

Keywords: Obesity-related cancer, Cancer stem cells, Leptin, Chemoresistance, Breast cancer, Pancreatic cancer

Core tip: Obesity and its main mediator leptin, are implicated in many protumorigenic processes, with emerging evidence from both the literature and our work pointing to a significant role in the development of resistance to chemotherapies. Chemoresistance is a major concern in the field of cancer therapy as some cancers have no targeted therapies available. As obesity reaches epidemic proportions around the world, its impact on diseases like cancer and its treatment becomes more relevant. In this paper, we will discuss the current state of the literature regarding the influence of obesity and leptin on cancer treatment and the development of chemoresistance.