1.7. Metabolic reprogramming:
Changes in energy metabolism are one of the specifications of tumor cells since tumor cells proliferate abnormally and accordingly, are dependent on the increased adaptation to the nutritional microenvironment, which is operated by the metabolic reprogramming [112, 153]. Due to the glucose deficiency in the tumor microenvironment, the metabolism of cancer cells shifts to aerobic glycolysis (the Warburg effect) [154]. The final product of this metabolic process is lactate, which is associated with treatment resistance [112, 155]. According to some evidence, other metabolic features such as reversed Warburg effect, glutamine metabolism, and metabolic symbiosis can cause acquired or adaptive drug resistance and challenge anti-tumor treatment [156].
Evidence suggests that disordered metabolism is involved in metastasis and malignancy [111]. Severe reduction of amino acids such as glutamine, tryptophan, and arginine and high levels of glycolysis are observed in cancer cells [111]. The metabolic features of malignant cells are regulated by tumor metabolic stress, leading to acidity, nutrient deficiency, and oxygen competition in the TME [157]. Apart from epigenetic and genetic alterations of cancer cells, the interactions between various components of TME and metabolic competition contribute to drug resistance and the growth and metastasis of tumor cells [158, 159].