Multidrug Resistance (MDR) refers to mechanisms by which many cancers develop resistance to chemotherapy drugs and is a major factor in the failure of many forms of chemotherapy. It affects patients with a variety of blood cancers and solid tumors, including breast, ovarian, lung, and lower gastrointestinal tract cancers. Tumors usually consist of mixed populations of malignant cells, some of which are drug-sensitive while others are drug-resistant. Chemotherapy kills drug-sensitive cells, but leaves behind a higher proportion of drug-resistant cells. As the tumor begins to grow again, chemotherapy may fail because the remaining tumor cells are now able to recognize the chemotherapy and reject it at the cellular level, thus rendering it resistant to the therapy.
This resistance to therapy is often the result of molecular “pumps” in tumor-cell membranes that actively expel chemotherapy drugs from the interior. This allows tumor cells to avoid the intended toxic effects of the drug.
As MDR begins to counteract chemotherapy drugs, it can require higher and higher doses to kill tumor cells, yet the unwanted side effects of the drugs, like cardiotoxicity, ultimately prevent such increases in dosing.
Two kinds of pumps commonly responsible for multidrug resistance in cancer are P-glycoprotein (P-gp) and the so-called multidrug resistance–associated protein (MRP). Because of their role in MDR, they have been the targets of several anticancer efforts. Unfortunately, efforts to block the activity of these pumps have resulted in serious side effects because they also play an important role in normal cell function.
Our most advanced therapy, Annamycin, represents a much-needed breakthrough in the battle against multidrug resistance. Its unique design prevents it from being recognized by MDR pumps, allowing Annamycin to avoid the multidrug resistance mechanisms that often defeat current therapies.