Mechanisms of anticancer drug resistance.

Chemotherapy agents are extremely important in the treatment of liquid malignancies, such as lymphoma, myeloma, and chronic lymphocytic leukemia. In addition, chemotherapy agents have proven effective in the adjuvant treatment of solid tumors, such as osteosarcoma, hemangiosarcoma, transitional cell carcinoma, and others. Unfortunately, chemotherapy resistance in these situations is the most significant cause of treatment failure. Therefore, the ability to predict, treat, or circumvent resistance is extremely likely to improve clinical outcomes. This article has reviewed the most widely investigated forms of chemotherapy resistance, such as reduced drug accumulation, increased DNA damage repair, decreased apoptosis, and others; however, new mechanisms are being found at an alarming pace. In addition, investigations to date have routinely centered on single-cell mechanisms of drug resistance, and cancer is truly a three dimensional disease. The elucidation of mechanisms surrounding (1) how tumors interact with their normal microenvironment, (2) how tumors interact in a three-dimensional environment, and (3) a better understanding of basic tumor physiology and biology may supersede in importance those previously elucidated single-cell mechanisms of chemoresistance.