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 Gastrointest Oncol. Feb 15, 2024; 16(2): 259-272 Published online Feb 15, 2024. doi: 10.4251/wjgo.v16.i2.259
Biological factors driving colorectal cancer metastasis
Shuai-Xing An, Zhao-Jin Yu, Chen Fu, Min-Jie Wei, Long-Hai Shen
Shuai-Xing An, Zhao-Jin Yu, Chen Fu, Min-Jie Wei, Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, Liaoning Province, China
Shuai-Xing An, Zhao-Jin Yu, Chen Fu, Min-Jie Wei, Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110122, Liaoning Province, China
Shuai-Xing An, BD Department, Greenpine Pharma Group Co., Ltd, Tianjin 300020, China
Long-Hai Shen, Center of Oncology, Genertec Liaoyou Gem Flower Hospital, PanJin 124010, Liaoning Province, China
Author contributions: An SX and Yu ZJ designed the article; An SX and Fu C performed the literature search and drafted the work; Shen LH and Wei MJ revised the work; and all authors are responsible for obtaining written permission to use any copyrighted text and/or illustrations.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
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/
Received: October 1, 2023 Peer-review started: October 1, 2023 First decision: December 11, 2023 Revised: December 23, 2023 Accepted: January 8, 2024 Article in press: January 8, 2024 Published online: February 15, 2024 Processing time: 123 Days and 9.9 Hours
Abstract
Approximately 20% of colorectal cancer (CRC) patients present with metastasis at diagnosis. Among Stage I-III CRC patients who undergo surgical resection, 18% typically suffer from distal metastasis within the first three years following initial treatment. The median survival duration after the diagnosis of metastatic CRC (mCRC) is only 9 mo. mCRC is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue, allowing cancer cells to spread from primary to distant organs; however, increasing evidence suggests that the mCRC process can begin early in tumor development. CRC patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological alterations. Different genomic and nongenomic events can induce subclone diversity, which leads to cancer and metastasis. Throughout the course of mCRC, metastatic cascades are associated with invasive cancer cell migration through the circulatory system, extravasation, distal seeding, dormancy, and reactivation, with each step requiring specific molecular functions. However, cancer cells presenting neoantigens can be recognized and eliminated by the immune system. In this review, we explain the biological factors that drive CRC metastasis, namely, genomic instability, epigenetic instability, the metastatic cascade, the cancer-immunity cycle, and external lifestyle factors. Despite remarkable progress in CRC research, the role of molecular classification in therapeutic intervention remains unclear. This review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.
Core Tip: Metastatic colorectal cancer (CRC) is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue, allowing cancer cells to spread from primary to distant organs; however, increasing evidence suggests that this process can begin early during tumor development. CRC patients exhibit high heterogeneity and diverse cancer phenotypes that are classified based on molecular and morphological alterations. Different genomic and non-genomic events can induce sub-clone diversity, which leads to cancer and metastasis.