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].