The rationale for targeting GPER in cancer stems from the epidemiologic observation that female sex and history of pregnancy are associated with decreased incidence of and improved stage-specific survival for many common cancers, including melanoma, pancreatic ductal adenocarcinoma (PDAC), non–small cell lung cancer, leukemias, and colon carcinomas, among others (6–13). The gene discussed is GPER1; the disease is cancer.