Protein kinase D has emerged as a novel, targetable driver of Epithelial Ovarian Cancer!! Our lab has done well!!!!!

This work earned Ms. Komal Tyagi & Ms. Abha Sachdeva their Ph.D.! Epithelial ovarian cancer, especially high-grade serous ovarian cancer (HGSOC) remains deadliest gynecological malignancy due to lack of early-detection biomarkers and chemoresistance. Protein kinase D (PKD1-3), a member of diacylglycerol (DAG)-targeting, Ca++-Calmodulin family of serine/threonine kinases emerged as a novel, targetable driver of HGSOC. This review synthesizes significance of currently discovered molecular mechanisms of PKD-driven carcinogenesis of the ovary, promise of CRT0066101, a highly selective, potent PKD inhibitor as excellent anti-cancer agent and critically discussed importance of unidentified PKD substrates as novel pathobiological effectors and therapeutic targets in HGSOC. Mechanistically, PKD2 and PKD3 modulated Runx2 via MAPK/ERK1/2 pathway to drive HGSOC cell proliferation, EMT, migration/invasion and regulated Aurora kinase A via ERK signalling to induce uncontrolled G2/M cell cycle transition, mitosis and highly aggressive, chemoresistant neuroendocrine transdifferentiation.