Therapeutic targeting of GSC pathways and receptors, such as Notch, Wnt, SHH, EGFR, PDGFR, and VEGFR presented in this review, which are critically implicated in tumor cell proliferation, maintenance, and resistance to current therapies, is of significant interest as it provides reliable and physiologically relevant trials to block these stem cells via the inhibition of pathways and receptors. This evidence concerns the gene SHH and neoplasm.