Modulation of NR4A1–NR4A3 receptors as therapeutic targets in cancer biology reveals a novel category of mechanism-based therapies, and future efforts, due to their dichotomous responses, should involve meticulous evaluation of the cancer cell type targeted and moreover the method(s) of drug delivery, given the tissue- and cell-specific functional roles that NR4A receptors display in controlling cancer biology. This evidence concerns the gene NR4A1 and cancer.