Renal medullary carcinoma (RMC) is characterized by the complete loss of the SMARCB1 tumor suppressor, and it predominantly affects individuals with sickle cell trait (SCT), characterized by increased sickling of red blood cells in the renal medulla. It has been previously demonstrated that RMC tumors show a hypoxia signature, and in a recent study, researchers from MD Anderson Cancer Center aimed to investigate the connection between SMARCB1 loss and hypoxia under the setting of SCT.