LXS196 for Metastatic Uveal Melanoma - finally some progress

Abstract

Metastatic uveal melanoma continues to have a poor prognosis with distinct pathophysiology from cutaneous melanoma and limited effective treatment options. Targeted therapy with darovasertib towards protein kinase C is well tolerated with signals of early efficacy, warranting further exploration and combination strategies.

Fig. 1. PKC and MET activation signal growth through MAPK pathway via RAS activation.

GPCR   G-protein-coupled receptor, GTP   guanosine triphosphate, GDP   guanosine diphosphate, TRIO   guanine nucleoside exchange factor, PLCβ   phospholipase C beta, PIP2   phosphatidylinositol diphosphate, IP₃   inositol triphosphate, DAG   diacylglyceraol, PKC   protein kinase C, RasGRP3 RAS guanyl-releasing protein-3, RAS   Rat sarcoma virus, RAF   Rapidly accelerated fibrosarcomae, MEK   mitogen-activated protein kinase kinase, ERK   extracellular signal-regulated kinases, HGF   hepatocyte growth factor, c-MET   mesenchymal epithelial transition, GAB1  Grb2-associated binder 1, SHP2   Src homology 2 domain-containing, GRB2, growth factor receptor-bound protein 2, SOS   son of sevenless, PI3K  phosphatidylinositol 3-kinase, STAT   signal transducer and activator of transcription, FAK   focal adhesion kinase, AKT   protein kinase B, mTOR mechanistic target of rapamycin.