Cell culture, mouse studies offer potential new targets for cancer treatments

By The Science Advisory Board staff writers

August 30, 2022 -- University of Gothenburg scientists have identified a previously unknown mechanism controlling tumor growth in cultured cells and mice, potentially enabling future development of new drugs targeted at a range of cancers.

In an article, published August 29 in the journal Nature Communications, the researchers describe how a protein -- known as HnRNPK -- binds to the messenger RNA (mRNA) of the genes IER3 and IER3-AS1, preventing double-strand RNA from forming between them and keeping them separate.

"Keeping these two genes' RNA separate promotes growth of tumors that depend on growth factors. Without the HnRNPK protein, the properties that promote tumor growth are neutralized, paving the way for development of drugs that block the HnRNPK," Chandrasekhar Kanduri, PhD, professor of medical genetics at Sahlgrenska Academy at the University of Gothenburg, said in a statement.

The researchers note that "substantial evidence has accumulated" over the last few years supporting aberrant fibroblast growth factor (FGF) signaling, underlying the pathogenesis of multiple cancer types. They contend that their discovery "affords scope" for indirectly influencing FGF-2 (fibroblast growth factor 2), which is critical to both to the process in which stem cells mature into various cell types and to early embryonic development.

"Given the crucial role of FGF-2 in normal human development, using drugs that target the growth factor directly would have too many side effects. The mechanism we've now identified is part of the same signaling chain, but further downstream. So, the mechanism has the potential to become a more attractive cancer treatment option, with fewer side effects," said corresponding author Meena Kanduri, PhD, associate professor (docent) of molecular medicine at Sahlgrenska Academy.

The authors acknowledge that more research is needed to verify the transferability of their finding from cell culture and mouse studies to humans. Going forward, they plan to conduct studies to assess in more detail how the two genes regulated by FGF-2 govern the growth environment of tumors.

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