Title:Obesity and Inflammation: Colorectal Cancer Engines
Volume: 15
Author(s): Lara J. Bou Malhab*Wael M. Abdel-Rahman
Affiliation:
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
Keywords:
Chemotherapy, chronic inflammation, colorectal cancer, microenvironment, obesity, STAT3 signaling pathway.
Abstract: The prevalence of obesity continues to increase to the extent that it became a worldwide
pandemic. An accumulating body of evidence has associated obesity with the development of different
types of cancer, including colorectal cancer, which is a notorious disease with a high mortality
rate. At the molecular level, colorectal cancer is a heterogenous disease characterized by a myriad
of genetic and epigenetic alterations associated with various forms of genomic instability (detailed
in Supplementary Materials). Recently, the microenvironment has emerged as a major factor
in carcinogenesis. Our aim is to define the different molecular alterations leading to the development
of colorectal cancer in obese patients with a focus on the role of the microenvironment in carcinogenesis.
We also highlight all existent molecules in clinical trials that target the activated pathways
in obesity-associated colorectal cancer, whether used as single treatments or in combination.
Obesity predisposes to colorectal cancer via creating a state of chronic inflammation with dysregulated
adipokines, inflammatory mediators, and other factors such as immune cell infiltration. A unifying
theme in obesity-mediated colorectal cancer is the activation of the PI3K/AKT,
mTOR/MAPK, and STAT3 signaling pathways. Different inhibitory molecules towards these pathways
exist, increasing the therapeutic choice of obesity-associated colon cancer. However, obese
patients are more likely to suffer from chemotherapy overdosing. Preventing obesity through maintaining
a healthy and active lifestyle remains to be the best remedy.
