Dopamine D1 Receptor in Cancer

SIMPLE SUMMARY: Circulating hormones and their specific receptors play a significant role in the development and progression of various cancers. This review aimed to summarize current knowledge about the dopamine D1 receptor’s biological role in different cancers, including breast cancer, central nervous system tumors, lymphoproliferative disorders, and other neoplasms. Treatment with dopamine D1 receptor agonists was proven to exert a major anti-cancer effect in many preclinical models. We highlight this receptor’s potential as a target for the adjunct therapy of tumors and discuss possibilities and necessities for further research in this area. ABSTRACT: Dopamine is a biologically active compound belonging to catecholamines. It plays its roles in the human body, acting both as a circulating hormone and neurotransmitter. It acts through G-protein-coupled receptors divided into two subgroups: D1-like receptors (D1R and D5R) and D2-like receptors (D2R, D3R, D4R). Physiologically, dopamine receptors are involved in central nervous system functions: motivation or cognition, and peripheral actions such as blood pressure and immune response modulation. Increasing evidence indicates that the dopamine D1 receptor may play a significant role in developing different human neoplasms. This receptor’s value was presented in the context of regulating various signaling pathways important in tumor development, including neoplastic cell proliferation, apoptosis, autophagy, migration, invasiveness, or the enrichment of cancer stem cells population. Recent studies proved that its activation by selective or non-selective agonists is associated with significant tumor growth suppression, metastases prevention, and tumor microvasculature maturation. It may also exert a synergistic anti-cancer effect when combined with tyrosine kinase inhibitors or temozolomide. This review provides a comprehensive insight into the heterogeneity of dopamine D1 receptor molecular roles and signaling pathways in human neoplasm development and discusses possible perspectives of its therapeutic targeting as an adjunct anti-cancer strategy of treatment. We highlight the priorities for further directions in this research area.