Collectively, these data suggest that KLHDC8A is a regulator of hedgehog signaling and primary cilia formation and that targeting KLHDC8A through combinatorial SMO and Aurora B/C kinase inhibition is a promising therapeutic strategy for glioblastoma, serving as a potential therapeutic opportunity for targeting a previously undruggable target in glioblastoma. The gene discussed is KLHDC8A; the disease is glioblastoma.