Dual-drug regimen halts growth of treatment-resistant prostate tumors in preclinical studies
Researchers discovered that combining BET bromodomain inhibitors with DNA-methyltransferase inhibitors markedly slows the growth of prostate cancers that have switched cellular identity to evade therapy.
Scientists at Michigan Medicine identified a vulnerability in prostate cancers that become treatment-resistant by undergoing transdifferentiation, a process where tumor cells lose glandular features and adopt stem-cell characteristics. By pairing BET bromodomain inhibitors, which block alternative identity programs, with DNA-methyltransferase (DNMT) inhibitors that reactivate silenced glandular genes, they achieved a stronger suppression of tumor growth than either agent alone.
Preclinical experiments using cell lines and mouse xenografts demonstrated significant tumor shrinkage at reduced drug doses without notable toxicity. The researchers plan to pinpoint the key genes responsible for the effect and develop biomarkers to select patients most likely to benefit. Future clinical trials will test whether this strategy can prevent or reverse transdifferentiation in prostate cancer and possibly other cancers with similar cellular shifts.
Why it matters
The finding could lead to new therapies for aggressive prostate cancers that no longer respond to existing hormone treatments.
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