Resistance to chemotherapy: short-term drug tolerance and stem cell-like subpopulations.

Personalized medicine in cancer treatment has been a major goal for decades. Recently, the development of several therapies that specifically target key genetic alterations in different malignancies has dramatically improved patient outcome and brought the goal of personalized medicine closer to practicality. Despite the improved specificity of these treatment options, resistance to targeted therapy is common and remains a major obstacle to long-term management of a patient's disease. Often patient relapse is a result of the positive selection of cells with certain genetic alterations that result in a bypass of the therapeutic intervention. Once this occurs, patient relapse is inevitable and further treatment options are limited. The time to relapse is often quite rapid indicating that cancer cells may be primed for adapting to cytotoxic stimuli. Recently, it has been suggested that small subpopulations of cells allow resistance to occur more rapidly. It is thought that these cells are capable of surviving strong apoptotic stimuli until more permanent mechanisms of long-term resistance are developed. In order to decrease the rate of patient relapse, more studies are required in order to identify these subpopulations of cells, understand the mechanisms underlying their drug tolerance, and develop strategies to prevent them from evading treatment.