Fig. 2.

Mechanisms by which drug resistance is conferred in cancer. (In clockwise manner starting with defective apoptotic pathway) (1) the apoptotic pathway (p53 pathway) might be defective, which leads to various downstream resistance mechanisms like upregulation of Nrf2 expression, MGM2 upregulation, increased cell proliferation, etc.; (2) drug resistance is seen when there is increased or defective immune system function where hypersensitivity is observed; (3) a plethora of epigenetic factors play roles in conferring drug resistance in cancer; (4) when the detox systems (ROS, homeostasis) are activated, there is a detox of the drug from the cancer cell; (5) drug delivery problems: too low concentration or higher molecule size than required; (6) drug alteration by intrinsic enzymes or other proteins; (7) transporters of the cell membrane exhibit increased drug efflux or decreased influx; (8) even if the drug enters the cell and affects the genetic machinery, there is an increased intrinsic DNA repair mechanisms; (9) drug resistance is also seen during increased metabolism in liver