New combination of antibodies leads to more effective tumor destruction
"FOXM1 is a key factor that makes breast cancer and many other cancers more aggressive and more difficult to treat," Benita Katzenellenbogen said. "Because it is a master regulator of cancer growth and metastasis, there has been great interest in developing compounds that would be effective in blocking it."
So far, no successful drug agents have been developed to reduce the effects of FOXM1, John Katzenellenbogen said.
"There are reports of other inhibitors of FOXM1, but these are generally less potent and do not work well in the body," he said. "Our compounds have good anti-tumor activity in animal models. They behave well in vivo and have long half-lives in the blood. Some work well when given orally, which is desirable for ultimate patient use."
The researchers developed the new drugs by analyzing the properties of various compounds in a chemical library of potentially therapeutic agents. They selected those that reduced breast cancer cell proliferation and inhibited the expression of genes known to be regulated by FOXM1.
The team then modified the compounds to enhance their inhibition of FOXM1 and increase their cellular potency. Three of the tested compounds performed best.
We found that these compounds inhibit the growth of breast cancer cells that represent the major subtypes of breast cancers, including estrogen receptor-positive, HER2-positive and triple-negative breast cancers. They also block the growth of human breast tumors in mouse models." Benita Katzenellenbogen, professor of molecular and integrative physiology, University of Illinois
The research is promising, but preliminary, the scientists said. Full development of new anti-cancer drug agents can take more than a decade from this stage of discovery.
"Because cancers are often treated with a combination of drugs, we are exploring how our FOXM1 inhibitors might be combined with other standard-of-care agents to improve cancer treatment," Benita Katzenellenbogen said. Source:
University of Illinois at Urbana-Champaign Journal reference:
Ziegler, Y., et al. (2019) Suppression of FOXM1 activities and breast cancer growth in vitro and in vivo by a new class of compounds. npj Breast Cancer . doi.org/10.1038/s41523-019-0141-7 .
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