Al Bitar S, El-Sabban M, Doughan S, Abou-Kheir W. Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond. World J Gastroenterol 2023; 29(9): 1395-1426 [PMID: 36998426 DOI: 10.3748/wjg.v29.i9.1395]
Corresponding Author of This Article
Wassim Abou-Kheir, MSc, PhD, Associate Professor, Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Bliss St, Beirut 1107-2020, Lebanon. wa12@aub.edu.lb
Research Domain of This Article
Biochemistry & Molecular Biology
Article-Type of This Article
Review
Open-Access Policy of This Article
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/
World J Gastroenterol. Mar 7, 2023; 29(9): 1395-1426 Published online Mar 7, 2023. doi: 10.3748/wjg.v29.i9.1395
Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond
Samar Al Bitar, Marwan El-Sabban, Samer Doughan, Wassim Abou-Kheir
Samar Al Bitar, Marwan El-Sabban, Wassim Abou-Kheir, Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
Samer Doughan, Department of Surgery, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
Author contributions: Al Bitar S designed and wrote the first draft of the paper and collected and analyzed the data; El-Sabban M, Doughan S, and Abou-Kheir W are co-senior authors and contributed to conception and reviewed and edited the paper; Al Bitar S, El-Sabban M, Doughan S, and Abou-Kheir W provided the final approval of the version to be published.
Conflict-of-interest statement: All authors declare no conflicts of interest 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: Wassim Abou-Kheir, MSc, PhD, Associate Professor, Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Bliss St, Beirut 1107-2020, Lebanon. wa12@aub.edu.lb
Received: September 13, 2022 Peer-review started: September 13, 2022 First decision: September 29, 2022 Revised: October 12, 2022 Accepted: November 16, 2022 Article in press: November 16, 2022 Published online: March 7, 2023
Abstract
Colorectal cancer (CRC) is the third most diagnosed malignancy and a major leading cause of cancer-related deaths worldwide. Despite advances in therapeutic regimens, the number of patients presenting with metastatic CRC (mCRC) is increasing due to resistance to therapy, conferred by a small population of cancer cells, known as cancer stem cells. Targeted therapies have been highly successful in prolonging the overall survival of patients with mCRC. Agents are being developed to target key molecules involved in drug-resistance and metastasis of CRC, and these include vascular endothelial growth factor, epidermal growth factor receptor, human epidermal growth factor receptor-2, mitogen-activated extracellular signal-regulated kinase, in addition to immune checkpoints. Currently, there are several ongoing clinical trials of newly developed targeted agents, which have shown considerable clinical efficacy and have improved the prognosis of patients who do not benefit from conventional chemotherapy. In this review, we highlight recent developments in the use of existing and novel targeted agents against drug-resistant CRC and mCRC. Furthermore, we discuss limitations and challenges associated with targeted therapy and strategies to combat intrinsic and acquired resistance to these therapies, in addition to the importance of implementing better preclinical models and the application of personalized therapy based on predictive biomarkers for treatment selection.
Core Tip: Efforts in cancer research has yielded significant advances in our understanding of the molecular mechanisms underlying colorectal cancer (CRC) resistance and metastasis. Therapeutic strategies centered on targeted molecules involved in CRC progression have been shown to be highly promising in overcoming resistance to conventional treatments. Targeted agents are currently being evaluated in preclinical and clinical studies to identify novel pharmacological targets and to study the efficacy of personalized medicine-based approaches.
