Dopamine Receptors in Cancer: Are They Valid Therapeutic Targets?

Abstract

The dopamine receptors (DRs) family includes 5 members with differences in signal transduction and ligand affinity. Abnormal DRs expression has been correlated multiple tumors with their clinical outcome. Thus, it has been proposed that DRs-targeting drugs—developed for other diseases as schizophrenia or Parkinson’s disease—could be helpful in managing neoplastic diseases. In this review, we discuss the role of DRs and the effects of DRs-targeting in tumor progression and cancer cell biology using multiple high-prevalence neoplasms as examples. The evidence shows that DRs are valid therapeutic targets for certain receptor/disease combinations, but the data are inconclusive or contradictory for others. In either case, further studies are required to define the precise role of DRs in tumor progression and propose better therapeutic strategies for their targeting.

Dopamine and dopamine receptor D1 as a novel favourable biomarker for hepatocellular carcinoma

“…DRD1 functions as a determinant for G protein coupling between Gs heterotrimers in a complex with three catechol-based agonists [ 27 ], a noncatechol agonist, and a positive allosteric modulator for endogenous dopamine [ 27 ]. An increasing number of researchers have elucidated that DRD1 is a key player in several cancers [ 5 , 9 , 28 ] and a potential valid therapeutic target for certain receptors in cancer therapies [ 5 , 17 ]. In this study, we characterized genomic heterogeneity, investigated transcriptional expression, uncovered genomic mutations and coexpressed genes, identified the hub gene network and prognostic implications, and established the tumour immune microenvironment landscape of multifocal HCC and its biomarker genes.…”

“…Over the years, many studies on HCC have examined the mechanisms underlying HCC biomarker identification. In recent years, growing evidence has demonstrated that the dopamine receptor gene family plays an essential role in tumour initiation and progression [ 5 , 6 ]. Dopamine and dopamine receptor D1 (DRD1), a key member of the dopamine receptor family, exert positive effects on lung cancer [ 7 ], pancreatic cancer [ 8 ], and glioblastoma [ 9 ].…”

“…Accumulating evidence has demonstrated that DRD1 plays vital roles in immune regulation, hormone secretion mediation, gene expression, metabolic profile regulation [ 12 ], stress-induced behaviours [ 13 ], addiction-like behaviours [ 14 ], and so on. Aberrant DRD1 expression has been validated to correlate with various tumours and to be involved in tumour cell migration [ 15 ], tissue inflammation [ 10 ], autophagy activation [ 16 ], tumour growth [ 6 ], tumour progression and cancer cell biology [ 5 ].…”

Evaluation of the Differences in the Expression of Biogenic Amine-Related mRNAs and Proteins in Endometrioid Endometrial Cancer

“…Interestingly, Prabhu et al reported an overexpression of the D2 receptor in endometrial cancer, which is an antagonist of the D5 receptor [ 54 ]. On the other hand, an overexpression of the D5 receptor has been shown in hepatocellular carcinoma, gastric cancer, and glioblastoma, which contributed to their development [ 55 ]. The results obtained in this study indicate a possible disturbance in the signal transduction with the participation of the dopamine D5 receptor.…”

miRNAs in the Expression Regulation of Dopamine-Related Genes and Proteins in Endometrial Cancer

“…Moreover, the receptors also differ in their binding affinity within these groups. DRD5 has a 10-fold higher affinity than DRD1, while DRD3 and DRD4 bind dopamine similarly, but more strongly than DRD2 [ 4 ].…”