New compounds developed to block cancer growth regulator FOXM1
A study has demonstrated the success of new compounds that prevent FOXM1, a transcription factor, from increasing cancer proliferation.
Researchers have developed new drug compounds that act against the pro-cancer activity of FOXM1, a transcription factor that regulates the activity of dozens of genes.
So far, no successful drug agents have been developed to reduce the effects of FOXM1. However, the new 1,1-diarylethylene mono-and diamine compounds were found to suppress tumour growth in human cells and in mouse models of several types of human breast cancer.
FOXM1 is a naturally occurring protein that increases the expression of genes that are important to cell proliferation and development. It plays an important role during early development but is usually present at very low levels in adult tissues.
According to the researchers from the University of Illinois at Urbana-Champaign, US, they focused on FOXM1 because it is found in higher abundance in cancer cells than in healthy human cells.
“FOXM1 is a key factor that makes breast cancer and many other cancers more aggressive and more difficult to treat,” said researcher Professor Benita Katzenellenbogen. “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.”
…these compounds inhibit the growth of breast cancer cells that represent the major subtypes of breast cancers”
The researchers developed the new drugs by analysing 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. They identified three of the tested compounds which performed the best.
“We found that these compounds inhibit the growth of breast cancer cells that represent the major subtypes of breast cancers, including oestrogen receptor-positive, HER2-positive and triple-negative breast cancers,” Katzenellenbogen said. “They also block the growth of human breast tumours in mouse models.”
“There are reports of other inhibitors of FOXM1, but these are generally less potent and do not work well in the body,” Professor John Katzenellenbogen, one of the researchers, said. “Our compounds have good anti-tumour activity in animal models. They behave well in vivo and have long half-lives in the blood.”
The research is promising, but preliminary, the scientists said, emphasising that full development of new anti-cancer drug agents can take more than a decade from this stage of discovery.
The results appear in NPJ Breast Cancer.
University of Illinois at Urbana-Champaign