Cancer stem cell hypothesis and gastric carcinogenesis: Experimental evidence and unsolved questions

Traditionally, the clonal evolution model has been used to explain gastric cancer (GC) growth dynamics. According to this model, GC cells result from multiple mutations over time resulting in a population of continually diversifying cells. This heterogeneity enables the survival of different clones under particular conditions allowing growth at metastatic locations or resistance to chemotherapeutics. Cancer stem cell (CSC) theory completely overturns this traditional understanding of cancer suggesting that only CSCs can self-renew and promote tumor growth. CSCs are relatively refractory to conventional therapies, thus explaining why anti-cancer therapies are far from curative and why relapses of cancer are frequent. The identification of the CSC component of a tumor might, thus, open new therapeutic perspective based on the selective targeting of this small population of cells. In this review we examine the current scientific evidence supporting the existence of CSC in gastric tumors and analyze the main unsolved questions of this difficult field of cancer research.