Jadyn Costello

Helios Scholar

Uveal melanoma (UM) is notable for being both the rarest form of melanoma and the most common type of eye cancer. Although some FDA-approved therapies exist, none have established themselves as the standard of care. Once UM metastasizes, treatment becomes particularly challenging, leading to a grim prognosis where half of the patients succumb within 10 years of diagnosis, underscoring a critical need for more effective treatments. The DepMap analysis has identified Cyclin-dependent kinase 7 (CDK7) as a crucial gene in UM. CDK7 is an enzyme involved in various cellular functions such as cell cycle progression, transcription, and cancer development. Dr. Sharma’s drug discovery lab has developed TGN-1062, a reversible inhibitor designed to block CDK7 and its downstream pathways that contribute to cancer persistence. ATP-detecting viability assays and western blotting were employed to evaluate the efficacy of TGN-1062 against UM cell lines. The results showed that TGN-1062 has an IC50 of approximately 1 μM across four tested cell lines. Additionally, western blot analysis indicated promising changes in the expression of CDK7-related biomarkers following treatment. These findings support the hypothesis that TGN-1062 disrupts UM cell health by inhibiting CDK7, demonstrating effective IC50 values in the low micromolar range and influencing relevant biomarkers.