More than analgesia: evidence for metabolic regulation by the kappa opioid receptor in triple-negative breast cancer

Emerging findings implicate relationships between the kappa opioid receptor (KOR), one of the canonical opioid receptors, and cancer pathogenesis. Tian and colleagues investigate the antitumour effects of KOR signalling in triple-negative breast cancer, a malignant breast cancer subtype that currently has few effective therapeutic options. Their multimodal study relates KOR gene expression to cancer progression in humans, and further demonstrates antitumour potential of the KOR agonist U69593, both in cell lines and a mouse model. Their findings show that KOR agonism modulates the urea cycle and might alter ammonia balance and metabolic homeostasis sufficiently to impact cancer cell survival and proliferation. These findings challenge us to think of the KOR not just as a mediator of analgesia, but also as a metabolic regulator. These findings align with principles of systems biology that therapeutic and toxic effects of drugs are mediated by complex downstream functional networks that often cross the boundaries of classic receptor pathways.