AI Article Synopsis
- Small cell lung cancer (SCLC) often shows initial good response to chemotherapy, but patients frequently experience recurrence shortly after treatment.
- Research indicates that the drugs leflunomide (Leflu) and teriflunomide (Teri) can inhibit SCLC cell growth by reducing DRP1 phosphorylation and mitochondrial fragmentation.
- Combining Teri with carboplatin (Carbo) or lurbinectedin (Lur) enhances the anti-tumor effects, suggesting that these combinations could be a promising approach for future SCLC clinical trials by targeting mitochondrial pathways.
Article Abstract
Although up to 80% small cell lung cancer (SCLC) patients' response is good for first-line chemotherapy regimen, most patients develop recurrence of the disease within weeks to months. Here, we report cytostatic effect of leflunomide (Leflu) and teriflunomide (Teri) on SCLC cell proliferation through inhibition of DRP1 phosphorylation at Ser and decreased mitochondrial fragmentation. When administered together, Teri and carboplatin (Carbo) act synergistically to significantly inhibit cell proliferation and DRP1 phosphorylation, reduce abundance of intermediates in pyrimidine pathway, and increase apoptosis and DNA damage. Combination of Leflu&Carbo has anti-tumorigenic effect . Additionally, lurbinectedin (Lur) and Teri potently and synergistically inhibited spheroid growth and depleted uridine and DRP1 phosphorylation in mouse tumors. Our results suggest combinations of Carbo and Lur with Teri or Leflu are efficacious and underscore how the relationship between DRP1/DHODH and mitochondrial plasticity serves as a potential therapeutic target to validate these treatment strategies in SCLC clinical trials.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237869 | PMC |
| http://dx.doi.org/10.1016/j.isci.2024.110132 | DOI Listing |
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