Published online Jan 26, 2022. doi: 10.4252/wjsc.v14.i1.76
Peer-review started: April 18, 2021
First decision: May 12, 2021
Revised: May 15, 2021
Accepted: December 21, 2021
Article in press: December 21, 2021
Published online: January 26, 2022
Gastric cancer (GC) is a primary cause of cancer-related mortality worldwide, and even after therapeutic gastrectomy, survival rates remain poor. The presence of gastric cancer stem cells (GCSCs) is thought to be the major reason for resistance to anticancer treatment (chemotherapy or radiotherapy), and for the development of tumor recurrence, epithelial–mesenchymal transition, and metastases. Additionally, GCSCs have the capacity for self-renewal, differentiation, and tumor initiation. They also synthesize antiapoptotic factors, demonstrate higher performance of drug efflux pumps, and display cell plasticity abilities. Moreover, the tumor microenvironment (TME; tumor niche) that surrounds GCSCs contains secreted growth factors and supports angiogenesis and is thus responsible for the maintenance of the growing tumor. However, the genesis of GCSCs is unclear and exploration of the source of GCSCs is essential. In this review, we provide up-to-date information about GCSC-surface/intracellular markers and GCSC-mediated pathways and their role in tumor development. This information will support improved diagnosis, novel therapeutic approaches, and better prognosis using GCSC-targeting agents as a potentially effective treatment choice following surgical resection or in combination with chemotherapy and radiotherapy. To date, most anti-GCSC blockers when used alone have been reported as unsatisfactory anticancer agents. However, when used in combination with adjuvant therapy, treatment can improve. By providing insights into the molecular mechanisms of GCSCs associated with tumors in GC, the aim is to optimize anti-GCSCs molecular approaches for GC therapy in combination with chemotherapy, radiotherapy, or other adjuvant treatment.
Core Tip: In recent years, cancer stem cells (CSCs) have become an extremely important subject in cancer biology. CSCs are considered to be a very small component of tumor tissues, which nevertheless have the capacity for self-renewal, differentiation, and epithelial–mesenchymal transition. CSCs can also explain the clinical phenomenon of resistance to chemotherapy or radiotherapy. Many studies have also found that CSCs are important for cancer initiation and metastasis and play a key role in cancer recurrence. Here, we review GCSC (gastric cancer stem cell)-targeting therapies in GC, including information on GCSC-surface/intracellular markers and GCSC-mediated pathways. This review also provides a brief description of the GCSC niche. Understanding the molecular mechanism of GCSC-targeting agents can help optimize the accuracy of diagnosis and prognosis and the selection of the most appropriate therapy for GC patients.