PRMT5 Inhibition Has a Potent Anti-Tumor Activity Against Adenoid Cystic Carcinoma of Salivary Glands

The study investigates the potential of PRMT5 inhibitors as a targeted therapy for adenoid cystic carcinoma (ACC) of the salivary glands, a rare and challenging-to-treat cancer. Using an AI-driven platform, PRMT5 was identified as a promising therapeutic target. The study involved 87 primary ACC samples and demonstrated that PRMT5 inhibitors (PRT543 and PRT811) showed significant anti-tumor activity in ACC cell lines, organoids, and patient-derived xenograft models. The inhibitors downregulated genes associated with ACC progression, such as MYB and MYC. Additionally, combining PRMT5 inhibitors with lenvatinib, a drug that targets upregulated genes in ACC, enhanced the anti-tumor effects. These findings support the development of PRMT5 inhibitors as a monotherapy or in combination with lenvatinib for ACC treatment, tailored to patients' molecular profiles.