Hello
The stem cell and cancer stem cell concept has important implications for cancer therapy. Add , cancer stem cells are responsible for maintaining tumour growth . So , I wonder about the existence of proofs effective therapeutic to eliminate cancer stem cells ?!
Cancer stem cells (CSCs) have significant capacity of self-renewal to occur recurrence and metastatic lesion from minimal residual disease (MRD). Further, CSCs have the resistance to oxidative stress, inflammational cytokines, hypoxic microenvironment. CD44 variant, one of the CSC markers, helps xCT transporter stabilization, thereby promoting the uptake of cysteine, which is the essential substrate of glutathione (GSH). Metabolic reprogramming characterized by aerobic glycolysis (Warburg effect) and glutaminolysis-induced mitochondrial metabolism is activated not only CSCs but also non-CSCs, but CD44-HIF1alpha axis contributes to the metabolic adaptive response in the case of CSCs.
conventional chemotherapy is considered to be partially responsible for the increase of CSCs in number in vivo. The recent Nature article entitled as “Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function” investigated into the drastic proliferation of mutant KRAS-driven pancreatic ductal adenocarcinoma CSCs utilizing the Tet-ON/OFF and ON system. Notably, they have also revealed the metabolic features of CSCs to depend more on mitochondria as compared with non-CSCs or before oncogene ablation.
Collectively, CSCs-targeting anti-tumor therapy does not necessarily prevent any possibility of tumor recurrence and invasion. In particular, malignant melanoma with high plasticity between CSCs and non-CSCs should be regarded different from the hierarchy cancer model. However, each population depends on the different signal or molecule to survive and proliferate.
It has recently been shown that CSCs of tongue squamous cancer depend on xCT-GSH axis, whereas non-CSCs on EGFR signal. That is why the combination of the inhibitor against xCT and EGFR results in the synergistic therapeutic effect both in vitro and in vivo.
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