"In their recent article, the researchers describe why, in most of the patients, ribavirin as well as the standard chemotherapeutic drug cytarabine (Ara-C), eventually become ineffective at killing cancer cells. "By studying drug resistant cancer cells from AML patients and head and neck tumors, we found that a gene called "GLI1" is dramatically overactive in these cells," explains Hiba Zahreddine, doctoral student in the laboratory of Katherine Borden and first author of the Nature article. "With the help of our colleagues at Pharmascience Inc. we were then able to show that this results in a specific chemical change to the drugs, that prevents their toxicity toward the cancer cells," continues Professor Borden. Fortunately, drugs that inhibit the activity of GLI1 are currently available and the scientists showed that these drugs could switch the cancer cells back into a ribavirin-sensitive state. It is hoped that when used in combination-therapy with ribavirin (or more standard chemotherapy), these drugs will prevent the development of drug resistance in patients. The team has now received approval from Health Canada to undertake a new clinical trial to test the novel drug combination in AML patients."
Understanding and overcoming a novel type of anticancer drug resistance
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