Australian researchers from the Walter and Eliza Hall Institute (WEHI) have developed a novel approach to combat aggressive cancers by targeting a molecular process known as ‘minor splicing.’ Published in EMBO Reports, the study highlights how inhibiting minor splicing can significantly suppress tumor growth in liver, lung, and stomach cancers, particularly those driven by KRAS mutations, which are common in solid tumors. Minor splicing, although responsible for only 0.05% of RNA splicing, is crucial for the expression of about 700 genes, many of which are implicated in cancer cell proliferation.

The research demonstrated that blocking minor splicing leads to DNA damage in cancer cells and activates the p53 tumor suppressor pathway, causing cancer cell death while sparing healthy cells. This discovery opens the potential for a new class of cancer treatments that could be both more effective and less toxic. Using zebrafish, mouse models, and human lung cancer cells, the study is the first to show the impact of inhibiting minor splicing in vivo.

The team collaborated with the National Drug Discovery Centre to screen over 270,000 compounds, identifying potential inhibitors of minor splicing. The research underscores the potential of this strategy to provide broader cancer treatment options, particularly for patients with aggressive cancers that lack effective therapies.

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[Source: ScienceDaily, July 30, 2025]

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