London: Researchers at King’s College London have uncovered a novel strategy for treating certain aggressive blood cancers by targeting a once-overlooked part of the genome-so-called ‘junk DNA’-using existing cancer drugs. The approach could offer new hope for patients with limited treatment options.
According to Oman News Agency, the study, published in the journal ‘Blood’, focused on myelodysplastic syndrome (MDS) and chronic lymphocytic leukemia (CLL). These cancers are frequently driven by mutations in the ASXL1 and EZH2 genes, which normally help regulate gene expression. When mutated, they disrupt normal cell growth controls, leading to cancer.
Conventional treatments often target harmful proteins produced by faulty genes. But when those proteins are entirely absent-as is the case with these mutations-such drugs are ineffective. The research team turned their attention instead to transposable elements (TEs), repetitive DNA sequences that make up nearly half the human genome and were long considered genetic ‘junk.’
They discovered that in cancer cells with ASXL1 or EZH2 mutations, these TEs become highly active, causing genomic instability and DNA damage. This vulnerability creates an opportunity for intervention using PARP inhibitors-drugs already approved for other cancers, such as those involving BRCA mutations.
Typically, PARP inhibitors work by blocking DNA repair pathways. In this context, however, they exploit the TE-induced DNA damage by preventing cancer cells from repairing breaks caused by mobile genetic elements. This leads to an accumulation of lethal damage and cell death.
To validate the mechanism, researchers used reverse transcriptase inhibitors to suppress TE activity. Doing so nullified the effect of the PARP inhibitors, confirming that the drugs were acting specifically through this TE-mediated pathway.
Although the study concentrated on MDS and CLL, the findings may extend to other cancers with similar genetic defects, potentially expanding the use of PARP inhibitors and offering a new therapeutic angle for malignancies currently lacking effective treatments.