The uniqueness of our study is that we have (1) extended these findings to melanoma, (2) utilized CRISPR-Cas9 vs. CD133 siRNAs employed in previous studies, (3) used an inducible CD133 expression system, (4) examined downstream apoptotic events (caspases and their substrates), (5) utilized pharmacological inhibitors (BCL-2) and siRNAs (AKT), along with altered CD133 expression to determine the feasibility of combinatorial therapies for melanoma, and (6) examined the response to both chemotherapeutic agents (DTIC) and kinase inhibitors (trametinib). The gene discussed is PROM1; the disease is melanoma.