A hidden weakness in deadly cancers could lead to powerful new treatments — SkimNews
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- UCLA researchers found that small cell neuroendocrine cancers of the lung, prostate, and ovary — all characterized by loss of the RB tumor-suppressor gene — become critically dependent on the E2F3 protein to survive.
- The team identified the vulnerability using genome-wide CRISPR screens run on engineered human prostate cell organoids, which surfaced roughly 1,400 genes essential to cancer survival; E2F3 emerged as a shared dependency across all three organ types tested.
- Reducing E2F3 in RB-deficient cancer cells halted tumor division and in some cases killed the cells outright through synthetic lethality — the cells can survive loss of RB or E2F3 alone, but not both at once.
- DHODH inhibitors including the FDA-approved leflunomide and teriflunomide — currently used for autoimmune diseases — lowered E2F3 levels and slowed tumor growth in lab models, pointing to a potential drug-repurposing route.
- Senior author Dr. Owen N. Witte noted that survival statistics for these cancers have not meaningfully changed in more than 50 years, framing the discovery as a long-overdue opening for fresh treatment strategies.
- The study, published in Proceedings of the National Academy of Sciences, draws on more than a decade of work by Witte's lab to build laboratory models of small cell neuroendocrine prostate cancer.
Why it matters: Patients with small cell lung, prostate, and ovarian cancers face five-decade survival stagnation that Witte himself flags in the source, and the most actionable finding here is a repurposing angle: leflunomide and teriflunomide are already FDA-approved for autoimmune disease, so any eventual clinical translation could move faster than building a drug from scratch, though the work remains at the lab-model stage.
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