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Researchers have identified two drugs that are potent against acute myeloid leukemia (AML) when combined, but only weakly effective when used alone.
The research team was able to significantly enhance cancer cell death by jointly administering the drugs that are only partially effective when used as single-agent therapies. "Our study shows that two types of drugs, MDM2 inhibitors and BET inhibitors, work synergistically to promote significant anti-leukemia activity," said researcher Peter Adams, Professor at the Sanford Burnham Prebys Medical Discovery Institute in the US. "The results were surprising because previous research had shown that each drug on its own had modest benefit against AML. The new research provides scientific rationale to advance clinical studies of the drug combination in patients with AML," Adams added in the study published in the journal Nature Communications. There are many types of AML, and different cases have different chromosome changes, gene mutations and epigenetic modifications, making it difficult for researchers to find novel therapies that will work for a substantial proportion of patients. Although much progress has been made toward finding effective treatments in recent years, the long-term overall survival has stagnated. According to the American Cancer Society, the five-year survival rate for adults with AML remains less than 30 per cent. Notably, TP53, the most frequently mutated gene in all human cancers, is found unaltered in about 90 per cent of AML patients, the researchers said. Since the product of the TP53 gene, p53, acts to suppress tumours, scientists have sought drugs that reactivate or boost its anti-cancer powers in AML, which should provide a clinical benefit. However, such drugs on their own have been disappointing in AML. "We were interested in combining MDM2 and BET inhibitors because each showed encouraging pre-clinical activity, but limited activity when given to patients as a single agent," said Adams. "Our research unexpectedly showed that like MDM2 inhibitors, BET inhibitors activate p53, but through a different pathway. BET inhibitors mute the power of a protein called BRD4, which we found is a p53 suppressor in AML," Adams added. --IANS vc/bg ( 356 Words) 2021-01-19-20:10:06 (IANS)
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