G protein-coupled receptors as promising targets in cancer

The G Protein-Coupled Estrogen Receptor (GPER): A Critical Therapeutic Target for Cancer

“…Collectively, these drugs serve as effective treatments for modulating a wide assortment of diseases affecting almost every known physiological system. Experimental data strongly support the idea that GPCRs play a critical role in cancer, which is consistent with their role in tissue homeostasis, and this has been reviewed in detail [137][138][139][140][141]. In brief, these data include (i) the demonstration of a link between excessive signaling by GPCR cancers such as Mas-1, angiotensin II metabolite, angiotensin-(1-7) neuropeptides, gut hormones, and neuroendocrine and digestive cancers; (ii) findings showing that the constitutively acting mutations (CAMs) of GPCRs are associated with head and neck squamous cell carcinoma, small-cell lung cancer, thyroid cancer, pancreatic cancer, and prostate cancer; and (iii) laboratory evidence pointing to the overexpression of the α1B adrenoceptor (α1B-AR) in rodent fibroblasts resulted in focus formation.…”

Molecular Properties and Therapeutic Targeting of the EBV-Encoded Receptor BILF1

“…In fact, 69 new drugs have been FDA-approved within the last 5 years, and, as of 2017, 320 drugs, of which 114 are novel drugs acting on 64 novel GPCRs, were under investigation in clinical trials. The diseases and GPCRs in focus are extremely diverse: Metabolic disorders such as hyperparathyroidism (calcium-sensing receptor) [148] and diabetes type 2 (GLP-1 receptor and GPR119 among others) [149]; psychiatric disorders such as schizophrenia (dopamine receptor D 2 ) [150]; central nervous system-related diseases such as multiple sclerosis (sphingosine 1-phosphate phosphate receptor 1) [151]; several types of cancer [1,152,153]; and viruses like HIV-1 (CCR5) [154].…”

“…Based on the link between previously presented vGPCRs (including BILF1) and tumorigenesis, the general druggability of GPCRs in the context of cancer is briefly outlined [152,153]. Research has revealed several mechanisms through which GPCRs can promote oncogenesis:…”

“…To date, it is not yet FDA-approved. GPCR-targeting anti-cancer drugs with FDA approval are mainly small molecules (sonidegib, vismodegib, cabergoline, raloxifene, brigatinib), but peptides (lanreaotide, degarelix, leuprolide) and mAbs (mogamulizumab, erenumab) are also currently in use [152,153]. The fact that there are already therapeutics targeting GPCRs in cancer-with many more to come-illustrates the general feasibility of GPCR targeting in this context, which could likely also be translated to vGPCR-positive malignancies.…”