Notably, targeting pivotal signaling networks, including receptor tyrosine kinase pathways, the Ras/Raf/mitogen-activated protein kinase (MAPK) cascade, the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) axis, Wnt/β-catenin signaling, the ubiquitin–proteasome degradation system, Hedgehog signaling, as well as pathways involving hTERT, PIK3CA, PYGO2, and NTRK, has facilitated the identification of novel therapeutic agents for the clinical management of HCC [3,4]. The gene discussed is PYGO2; the disease is hepatocellular carcinoma.