The combination of B-Raf proto-oncogene, serine/threonine kinase (BRAF) and MAPK/ERK kinase (MEK) inhibitors, the frontline care for BRAFV600E-mutant melanoma, was found to induce the pyroptosis of melanoma cells by blocking extracellular regulated kinase (ERK)1/2 signaling and subsequently activating the GSDME cleaver, caspase-3. The gene discussed is MARK2; the disease is melanoma.