Somatic Mutations and Immunotherapy Outcome with CTLA-4 Blockade in Melanoma

One of the greatest challenges in the study and treatment of cancer has been that the disease is too heterogeneous: too many tissue types, too many etiologic factors, too much genetic diversity. After the discovery of oncogenes, it was thought that a limited number of genes, the proto-oncogenes, might turn a normal cell into a cancerous one. But soon it was discovered that tumor-suppressor genes antagonize the action of oncogenes, thus increasing genetic diversity in the context of cancer pathogenesis. To date, about 140 genes have been identified that can drive cancer growth when genetically altered.1 The discovery that driver . . .