Fewer Side Effects: A New Potential Cancer Treatment Target

Targeting Cancer Cells Illustration

Future treatments that target the new mechanism could have fewer side effects than current treatments.

Researchers have discovered a potential new cancer treatment target.

University of Gothenburg researchers have identified a previously undiscovered mechanism that regulates tumor development in mice and cultured cells. This finding could eventually pave the way for the creation of new drugs to treat a variety of cancer diseases.

The researchers from Gothenburg detailed their findings in a study that was recently published in Nature Communications. It has to do with a protein that binds genetic material and, as the researchers have recently shown, is also in charge of characteristics that regulate tumor growth.

The protein, known as HnRNPK, binds to messenger RNA (mRNA), which is encoded by the genes IER3 and IER3-AS1. These genes are highly active in several types of cancer. The HnRNPK prevents double-stranded RNA from developing between these genes by binding to their mRNA.

Chandrasekhar Kanduri and Meena Kanduri

Chandrasekhar Kanduri and Meena Kanduri, Sahlgrenska Academy at the University of Gothenburg. Credit: Elin Lindström, University of Gothenburg

Changes in tumor growth

“Keeping these two genes’ RNA separate promotes the growth of tumors that depend on growth factors. Without the HnRNPK protein, the properties that promote tumor growth are neutralized, paving the way for the development of drugs that block the HnRNPK,” says Chandrasekhar Kanduri, Professor of Medical Genetics at Sahlgrenska Academy, University of Gothenburg, who is one of the research leaders behind the study.

The study also demonstrates that the HnRNPK protein binds to the mRNA of a number of other genes in a manner that prevents double-strand RNA from forming.

The finding opens up the possibility of indirectly regulating the growth factor FGF-2, which is widely known to be essential for both the process by which stem cells mature into various cell types and early embryonic development.

Fewer side effects

Meena Kanduri, Associate Professor (Docent) of Molecular Medicine at Sahlgrenska Academy, is the corresponding author of the article.

“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,” she says.

More research is needed to verify the transferability of the finding from cell culture and mouse studies to humans. In the next stage, the group plans to conduct extended studies to examine in more detail how the pair of genes regulated by FGF-2 govern the growth environment of tumors.

Reference: “HnRNPK maintains single strand RNA through controlling double-strand RNA in mammalian cells” by Sagar Mahale, Meenakshi Setia, Bharat Prajapati, Santhilal Subhash, Mukesh Pratap Yadav, Subazini Thankaswamy Kosalai, Ananya Deshpande, Jagannath Kuchlyan, Mirco Di Marco, Fredrik Westerlund, L. Marcus Wilhelmsson, Chandrasekhar Kanduri and Meena Kanduri, 29 August 2022, Nature Communications.
DOI: 10.1038/s41467-022-32537-0

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