Impact of Cancer Stem Cells on Therapy Resistance in Gastric Cancer

Abstract

Gastric cancer (GC) is the fourth leading cause of cancer death worldwide, with an average 5-year survival rate of 32%, being of 6% for patients presenting distant metastasis. Despite the advances made in the treatment of GC, chemoresistance phenomena arise and promote recurrence, dissemination and dismal prognosis. In this context, gastric cancer stem cells (gCSCs), a small subset of cancer cells that exhibit unique characteristics, are decisive in therapy failure. gCSCs develop different protective mechanisms, such as the maintenance in a quiescent state as well as enhanced detoxification procedures and drug efflux activity, that make them insusceptible to current treatments. This, together with their self-renewal capacity and differentiation ability, represents major obstacles for the eradication of this disease. Different gCSC regulators have been described and used to isolate and characterize these cell populations. However, at the moment, no therapeutic strategy has achieved the effective targeting of gCSCs. This review will focus on the properties of cancer stem cells in the context of therapy resistance and will summarize current knowledge regarding the impact of the gCSC regulators that have been associated with GC chemoradioresistance.

Isoliquiritigenin Inhibits Gastric Cancer Stemness, Modulates Tumor Microenvironment, and Suppresses Tumor Growth through Glucose-Regulated Protein 78 Downregulation

“…Cancer cells possessing the ability to self-renew and maintain stemness may cause cancer recurrence and contribute to chemoresistance. Suppression of cancer stemness may be a novel target for gastric cancer therapy in precision medicine [ 2 , 3 ].…”

Targeting Gastric Cancer Stem Cells to Enhance Treatment Response

“…They play a key role in cancer metastasis, recurrence, and chemotherapy resistance [ 13 , 14 , 15 , 16 ]. In view of the important role of CSCs in GC, many scholars believe that the key to the treatment of GC is to completely eliminate CSCs in gastric cancer [ 17 , 18 , 19 ] ( Figure 1 ). In order to improve the prognosis of patients with advanced GC, finding new drugs to target GCSCs may be the direction of therapy [ 20 , 21 ].…”

MAGE-A3 regulates tumor stemness in gastric cancer through the PI3K/AKT pathway

“…Recently, many studies have focused on a specific class of tumor cells, namely cancer stem cells. They are involved in most processes of disease progression and heterogeneity of tumor [ 5 ]. Cancer stem cells own some characteristics as normal stem cells, such as self-renewal and ability to differentiate into other cells that consist of various parts of the tumor [ 6 ].…”