Two-Pronged Drug Combination for Advanced Prostate Cancer: Fadraciclib Plus Ipatasertib (or Capivasertib)

Scientists at The Institute of Cancer Research in London have identified a combination therapy that may benefit up to 40 percent of men with advanced prostate cancer, particularly those whose tumors have become resistant to hormone therapies. This approach targets two proteins essential for cancer cell survival: MCL1 and AKT. Direct inhibition of MCL1 has proven challenging due to toxicity, so researchers used fadraciclib, a CDK9 inhibitor that indirectly reduces MCL1 levels. They paired this with AKT inhibitors, either ipatasertib or capivasertib, both drugs currently in clinical trials or approved for other cancers.

Laboratory studies showed that this combination triggers prostate cancer cell death, whereas using either drug alone had no significant effect on tumor growth. The most responsive tumors were those characterized by PTEN loss and PI3K activation, a subtype present in about 40 percent of advanced prostate cancers. In mouse models bearing these tumors, the combination therapy significantly slowed tumor growth and induced cancer cell apoptosis. The untreated tumors grew over sixfold in size within 10 days, while combination-treated tumors did not even double in that period.

The research team is actively seeking funding to advance these findings into clinical trials for prostate cancer patients. The combination holds promise not only for slowing tumor progression but also potentially reducing the development of treatment resistance. Since the individual drugs are already in late-stage development or approved for other indications, clinical translation may occur relatively quickly.

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