J Cancer 2021; 12(4):1125-1132. doi:10.7150/jca.50376 This issue

Review

GDF15/GFRAL Pathway as a Metabolic Signature for Cachexia in Patients with Cancer

Darakhshan Sohail Ahmed1,2, Stéphane Isnard1,2,3, John Lin1,2, Bertrand Routy4,5, Jean-Pierre Routy1,2,6✉

1. Infectious Disease and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Montreal, QC, Canada
2. Division of Hematology and Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada
3. CIHR Canadian HIV Trials Network, Vancouver, BC
4. Division of Hémato-oncologie, Centre hospitalier de l'Université de Montréal
5. Centre de recherche du Centre hospitalier de l'Université de Montréal
6. Division of Hematology, McGill University Health Centre, Montreal, QC, Canada

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Ahmed DS, Isnard S, Lin J, Routy B, Routy JP. GDF15/GFRAL Pathway as a Metabolic Signature for Cachexia in Patients with Cancer. J Cancer 2021; 12(4):1125-1132. doi:10.7150/jca.50376. Available from https://www.jcancer.org/v12p1125.htm

File import instruction

Abstract

Cachexia is a metabolic mutiny that directly reduces life expectancy in chronic conditions such as cancer. The underlying mechanisms associated with cachexia involve inflammation, metabolism, and anorexia. Therefore, the need to identify cachexia biomarkers is warranted to better understand catabolism change and assess various therapeutic interventions. Among inflammatory proteins, growth differentiation factor-15 (GDF15), an atypical transforming growth factor-beta (TGF-β) superfamily member, emerges as a stress-related hormone. In inflammatory conditions, cardiovascular diseases, and cancer, GDF15 is a biomarker for disease outcome. GDF15 is also implicated in energy homeostasis, body weight regulation, and plays a distinct role in cachexia. The recent discovery of its receptor, glial cell line-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL), sheds light on its metabolic function. Herein, we critically review the mechanisms involving GDF15 in cancer cachexia and discuss therapeutic interventions to improve outcomes in people living with cancer.

Keywords: GDF15, GFRAL, Inflammation, cachexia, cancer