Association of tumor cells chemoresistance mechanisms and suboptimal systemic cytotoxic treatment results

Abstract

Systemic cytotoxic chemotherapeutic treatment of malignant tumors does not fully meet its goal due to the resistance of present tumor cells to the applied therapy. Chemoresistance is complex and multifactorial, caused by numerous mechanisms that alter drug concentration in the cell, by changes in expression of the epidermal growth factor and by activation of intracellular signaling pathways PI3K / Akt and MAPK. The factor of chemoresistance is also an increased level of antioxidative glutathione and glutathione transferase – S enzyme and the presence of tumor stem cells that signifi cantly improve protection of DNA from damage. Apart from cellular factors, resistance is infl uenced by extracellular hypoxia and acidosis and autophagy. Overcoming the chemoresistance is possible by using nanomechanisms for delivery of drugs to tumor cells, autophagy inhibitors like antimalarials chloroquine and hydroxychloroquine and plant polyphenols. By bett er understanding the mechanisms of chemoresistance and it’s overcoming it can be possible to achieve improvement in antitumor treatment.