Combinational Inhibition of MEK and AKT Synergistically Induces Melanoma Stem Cell Apoptosis and Blocks NRAS Tumor Growth.

Malignant melanoma is a lethal skin cancer containing melanoma-initiating cells (MICs), implicated in tumorigenesis, invasion, and drug resistance, and characterized by an elevated expression of stem cell markers, including CD133. siRNA knockdown of CD133 has been previously shown to enhance apoptosis induced by the MEK inhibitor trametinib in melanoma cells. This study investigates the underlying mechanisms of CD133's anti-apoptotic activity in patient-derived BAKP melanoma, harboring the difficult-to-treat NRAS driver mutation, after CRISPR-Cas9 CD133 knockout or Doxycycline (Dox)-inducible re-expression of CD133.