Ren SN, Zhang ZY, Guo RJ, Wang DR, Chen FF, Chen XB, Fang XD. Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer. World J Gastroenterol 2023; 29(13): 1911-1941 [PMID: 37155531 DOI: 10.3748/wjg.v29.i13.1911]
Corresponding Author of This Article
Xue-Bo Chen, MD, Doctor, Professor, Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, Jilin Province, China. chenxb@jlu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
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/
Sheng-Nan Ren, Fang-Fang Chen, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
Zhan-Yi Zhang, Rui-Jie Guo, Da-Ren Wang, Bethune Third Clinical Medical College, Jilin University, Changchun 130021, Jilin Province, China
Xue-Bo Chen, Xue-Dong Fang, Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
Author contributions: Ren SN and Zhang ZY reviewed the literature and wrote the paper; Zhang ZY designed and draw the figures; Guo RJ, Wang DR, and Chen FF performed the collected data; Fang XD and Chen XB initiated the idea and revised the manuscript; all authors have read and approved the final manuscript.
Supported bythe Natural Science Foundation of Jilin Province, No. 20210101433JC.
Conflict-of-interest statement: Authors declare 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: Xue-Bo Chen, MD, Doctor, Professor, Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, Jilin Province, China. chenxb@jlu.edu.cn
Received: September 25, 2022 Peer-review started: September 25, 2022 First decision: January 3, 2023 Revised: February 2, 2023 Accepted: March 21, 2023 Article in press: March 21, 2023 Published online: April 7, 2023
Abstract
Colorectal cancer (CRC) is the most common digestive malignancy across the world. Its first-line treatments applied in the routine clinical setting include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, resistance to therapy has been identified as the major clinical challenge that fails the treatment method, leading to recurrence and distant metastasis. An increasing number of studies have been attempting to explore the underlying mechanisms of the resistance of CRC cells to different therapies, which can be summarized into two aspects: (1) The intrinsic characters and adapted alterations of CRC cells before and during treatment that regulate the drug metabolism, drug transport, drug target, and the activation of signaling pathways; and (2) the suppressive features of the tumor microenvironment (TME). To combat the issue of therapeutic resistance, effective strategies are warranted with a focus on the restoration of CRC cells’ sensitivity to specific treatments as well as reprogramming impressive TME into stimulatory conditions. To date, nanotechnology seems promising with scope for improvement of drug mobility, treatment efficacy, and reduction of systemic toxicity. The instinctive advantages offered by nanomaterials enable the diversity of loading cargoes to increase drug concentration and targeting specificity, as well as offer a platform for trying the combination of different treatments to eventually prevent tumor recurrence, metastasis, and reversion of therapy resistance. The present review intends to summarize the known mechanisms of CRC resistance to chemotherapy, radiotherapy, immunotherapy, and targeted therapy, as well as the process of metastasis. We have also emphasized the recent application of nanomaterials in combating therapeutic resistance and preventing metastasis either by combining with other treatment approaches or alone. In summary, nanomedicine is an emerging technology with potential for CRC treatment; hence, efforts should be devoted to targeting cancer cells for the restoration of therapeutic sensitivity as well as reprogramming the TME. It is believed that the combined strategy will be beneficial to achieve synergistic outcomes contributing to control and management of CRC in the future.
Core Tip: Mechanisms of Colorectal cancer (CRC) cell resistance can be attributed to tumoral and environmental factors, the former of which includes gene expression alteration, signaling pathway activation, metabolic rewiring, and the later refers to complicated adaptions regarding cancer associated fibroblast, immune cells, hypoxic conditions. Taking efforts to conquer therapeutic resistance is imperative to improve CRC patients` survival. Nanotechnology possesses distinct advantages to increase specificity of treatment and realize codelivery of multiple drugs, which facilitates to restore sensitivity to antitumor therapy, and modulate suppressive tumor microenvironment to stimulatory environment.
