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Australian Scientists Find New Way to Fight Aggressive Cancer by Blocking 'Minor Splicing'

Alexey Kryvenko, medical expert
Last reviewed: 03.08.2025

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28 July 2025, 19:54

Researchers at WEHI Medical Research Institute (Australia) have discovered a promising strategy to suppress the growth of hard-to-treat and aggressive tumours by blocking a specialised molecular process known as minor splicing. The work is published in EMBO Reports.

What is the essence of the discovery:

Blocking minor splicing significantly slows the growth of liver, lung and stomach tumors.
The strategy is particularly effective against cancers caused by mutations in the KRAS gene, one of the most common oncogenes.
At the same time, healthy cells are almost not damaged, which gives hope for a safer treatment.

What is minor splicing:

In the body, to make proteins, DNA is first converted to RNA, which is then cut up and processed in a process called splicing. Major splicing accounts for 99.5% of all activity. Minor splicing is a rare but essential mechanism that processes about 700 of the body’s 20,000 genes, including those that control cell growth and division.

This process has proven to be a weak point in cancer cells, especially in the presence of KRAS mutations. Its blocking:

causes accumulation of DNA damage in tumor cells;
activates the p53 anti-oncogenic pathway, which triggers cell division arrest or death.

Experiments:

The scientists used zebrafish, mouse and human lung cancer models. By reducing the levels of the protein RNPC3 (a key component of minor splicing), they were able to:

significantly slow down tumor growth;
activate the p53 defense mechanism;
achieve minimal harm to normal tissues.

What's next:

In collaboration with the National Center for Drug Development, the researchers have tested more than 270,000 molecules and have already found potential inhibitors of minor splicing.

"Our discovery changes the approach: instead of targeting specific mutations that not everyone has, we turn off a fundamental process that drives the growth of many cancers," said Professor Joan Heath, head of the WEHI laboratory.

Importance for the future:

A potential new class of drugs against aggressive cancers, including lung, liver and stomach cancer.
Prospects for the treatment of tumors with a functional p53 gene.
Fewer side effects compared to traditional chemotherapy.

The discovery was supported by the National Health and Medical Research Council of Australia, the Ludwig Institute for Cancer Research and the US National Institute of Neurological Disorders and Stroke (NINDS).