Scientists from the University of Michigan Comprehensive Cancer Center have investigated a new drug that showed the potential to address a rare kind of acute leukemia, revealing this molecule might also play a role in fighting prostate cancer.
Tomasz Cierpicki and Jolanta Grembecka have been working together to identify a small-molecule inhibitor with the ability to block the interaction between menin and MLL fusion proteins.
MLL fusion leukemia can occur in both children and adults and represents about 10 percent of acute leukemia in adults, and nearly 70 percent of acute leukemia in children. Currently available treatments are not effective, since only one-third of the patients survive more than 5 years.
It is particularly difficult to advance drugs that address protein-protein interactions like the menin-MLL fusion protein, part of the reason why they are called “undruggable” targets.
“In many types of cancer, you see multiple interactions and mutations that trigger the cancer. The MLL-menin interaction is a good drug target because it’s the primary driver in this type of leukemia. By blocking this interaction, it’s very likely to stop the cancer,” explained Dr. Grembecka, a professor from the University of Michigan Medical School in a press release.
Two compounds were tested both in mice with MLL leukemia and in cancer cell lines. The results, published in Cancer Cell, revealed these compounds could block MLL-menin interactions without damaging normal blood cells. Furthermore, the compounds were metabolized at a good rate and successfully delivered into the blood.
“Against all odds, we decided to explore finding a way to block the MLL-menin interaction with small molecules. From nothing, we have been able to identify and greatly improve a compound and show that it’s got valuable potential in blocking MLL fusion leukemia in animal models,” said Cierpicki from the U-M Medical School.
Importantly, the team discovered that MLL and menin play a role in androgen receptor signaling, a crucial driver of prostate cancer, highlighting a potential role in future prostate cancer therapies.
“Our study suggests that this MLL-menin inhibitor might also have a potential role in a more common solid tumor, in this case prostate cancer,” noted the senior author, Arul M. Chinnaiyan. These compounds will be further tested before any trials are considered.
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