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World J Gastroenterol. Sep 7, 2022; 28(33): 4744-4761
Published online Sep 7, 2022. doi: 10.3748/wjg.v28.i33.4744
Regulation of transforming growth factor-β signaling as a therapeutic approach to treating colorectal cancer
Jana Maslankova, Ivana Vecurkovska, Miroslava Rabajdova, Jana Katuchova, Milos Kicka, Michala Gayova, Vladimir Katuch
Jana Maslankova, Ivana Vecurkovska, Miroslava Rabajdova, Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef Safarik University in Kosice, Kosice 04011, Slovakia
Jana Katuchova, Milos Kicka, First Department of Surgery, Medical Faculty of Safarik University, Kosice 04011, Kosicky kraj, Slovakia
Michala Gayova, Department of Burns and Reconstructive Surgery, Medical Faculty at Safarik University and University Hospital, Kosice 04011, Slovakia
Vladimir Katuch, Department of Neurosurgery, Medical Faculty at Safarik University and University Hospital, Kosice 04011, Slovakia
Author contributions: Maslankova J, Vecurkovska I, Rabajdova M, Katuchova J, Kicka M, Gayova M, and Katuch V contributed equally to the study’s conception, design and undertaking, and to manuscript preparation; all authors have read and approve the final manuscript.
Conflict-of-interest statement: The authors declare having no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jana Katuchova, MD, PhD, Doctor, Professor, Surgeon, First Department of Surgery, Medical Faculty of Safarik University, 1 Trieda SNP, Kosice 04011, Kosicky kraj, Slovakia. jana.katuchova@upjs.sk
Received: May 12, 2022
Peer-review started: May 12, 2022
First decision: June 19, 2022
Revised: July 6, 2022
Accepted: August 16, 2022
Article in press: August 16, 2022
Published online: September 7, 2022
Processing time: 111 Days and 0.6 Hours
Abstract

According to data from 2020, Slovakia has long been among the top five countries with the highest incidence rate of colorectal cancer (CRC) worldwide, and the rate is continuing to rise every year. In approximately 80% of CRC cases, allelic loss (loss of heterozygosity, LOH) occurs in the long arm of chromosome 18q. The most important genes that can be silenced by 18q LOH or mutations are small mothers against decapentaplegic homolog (SMAD) 2 and SMAD4, which are intracellular mediators of transforming growth factor (TGF)-β superfamily signals. TGF-β plays an important role in the pro-oncogenic processes, including such properties as invasion, epithelial-mesenchymal transition (commonly known as EMT), promotion of angiogenesis, and immunomodulatory effects. Several recent studies have reported that activation of TGF-β signaling is related to drug resistance in CRC. Because the mechanisms of drug resistance are different between patients in different stages of CRC, personalized treatment is more effective. Therefore, knowledge of the activation and inhibition of factors that affect the TGF-β signaling pathway is very important.

Keywords: Small mothers against decapentaplegic homologs; Transforming growth factor-beta; Colorectal cancer; Marker; Signaling pathway

Core Tip: A thorough understanding of the complete transforming growth factor (TGF)-β/small mothers against decapentaplegic homolog signaling pathway is important for defining its functions during pathological processes of colorectal cancer. Inhibitors specifically targeting TGF-β pathway mediators that reduce the expression of a particular protein may lead to fewer/milder adverse effects. However, the dual role of the TGF-β pathway in the onset and progression of cancer complicates the physiological/ pathological and, thus, clinical situation. In recent years, research has shown that modification of members of this pathway is a promising approach for clinical procedures. Long-term treatment should emphasize personalized and targeted therapy.