Associate Professor Everardo Macias, PhD, was invited to deliver a Grand Rounds lecture at the Georgia Cancer Center in Augusta, Georgia, on Nov. 21, 2025. His presentation, “Investigating Understudied Kinases for Cancer Therapy and to Mitigate Off‑Target Toxicities,” highlighted two major research initiatives currently underway in his laboratory.
Macias first discussed his group’s work on NUvel (nua) AmP-activated protein kinase (AMPK)-related kinase 2 (NUAK2), an adenosine monophosphate-activated protein kinase (AMPK)‑family kinase that his team has identified as a key driver of neuroendocrine prostate cancer. NUAK2 is relatively understudied protein kinase that has been implicated to play roles in cell adhesion, migration, and stress response.
Their recently released preprint, “NUAK2 is a Therapeutically Tractable Regulator of RNA Splicing and Tumor Progression in Neuroendocrine Prostate Cancer,” underscores the strong therapeutic potential of targeting NUAK2 and reveals its mechanism of action as an mRNA splicing factor. Notably, the study demonstrates that an FDA‑approved drug exhibits potent off‑target inhibition of NUAK2, presenting an immediate opportunity for therapeutic repurposing.
Macias then presented his laboratory’s research on serine/threonine-protein kinase 3 (STK3), a kinase with dual and context‑dependent functions, acting as a tumor suppressor in normal tissues while promoting tumorigenesis in breast cancer. He described how his lab has developed small‑molecule compounds that can selectively modulate STK3 kinase activity. This strategy could help protect healthy tissues, like the heart, from the harmful side effects of chemotherapy, while concurrently slowing the growth of breast cancer tumors.