CTLA4 and cancer: Although the treatment of metastatic melanoma has been implemented by improvements in immunotherapy (viz., an anti-programmed cell death protein 1 (PD-1), anti-programmed death ligand-1 (PDL-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)) and targeted therapy (viz., BRAF and MEK Inhibitors) [155], unfortunately most patients develop therapeutic resistance associated with cancer progression and low survival rates [156].