CUP, cancer of unknown primary; MTB, molecular tumor board; PI3K, phosphoinositide 3-kinase; PARP, poly (ADP-ribose) polymerase; FGFR, fibroblast growth factor receptor; mTOR, mammalian target of rapamycin; HER2, human epidermal growth factor receptor 2; CDK, cyclin-dependent kinase; MEK, Mitogen-activated protein kinase kinase; MAPK, Mitogen-activated protein kinase; SMO, Smoothened; SOC, standard of care; TMB, tumor mutational burden; LOH, loss of heterozygosity. The gene discussed is SMO; the disease is cancer.