While several drugs are effective against multiple myeloma, including the proteasome inhibitor bortezomib, multiple myeloma cells are often able to survive by increasing the production of a protein known as Mcl-1. Mcl-1 regulates a number of processes that promote cell survival and has been implicated in resistance to anti-myeloma drugs that were initially effective. However, a team of researchers led by Xin-Yan Pei, M.D., Ph.D., and Steven Grant, M.D., recently published the findings of a study in the journal PLoS ONE demonstrating that a novel drug combination both reduces Mcl-1 expression and disrupts its interactions with other proteins to effectively kill multiple myeloma cells. The therapy combines a type of drug known as a Chk1 inhibitor with another called a MEK inhibitor. Chk1 inhibitors prevent cells from arresting in stages of the cell cycle that facilitate the repair of DNA damage, while MEK inhibitors prevent cells from activating a variety of proteins that regulate DNA repair processes while promoting the accumulation of pro-death proteins.
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