Abstract
Hundreds of G protein coupled receptor (GPCR) isotypes integrate and coordinate the function of individual cells mediating signaling between different organs in our bodies. As an aberration of the normal relationships that organize cells' coexistence, cancer has to deceive cell-cell communication in order to grow and spread. GPCRs play a critical role in this process. Despite the fact that GPCRs represent one of the most common drug targets, current medical practice includes only a few anticancer compounds directly acting on their signaling. Many approaches can be envisaged to target GPCRs involved in oncology. Beyond interfering with GPCRs signaling by using agonists or antagonists to prevent cell proliferation, favor apoptosis, induce maturation, prevent migration, etc., the high specificity of the interaction between the receptors and their ligands can be exploited to deliver toxins, antineoplastic drugs or isotopes to transformed cells. In this review we describe the strategies that are in use, or appear promising, to act directly on GPCRs in the fight against neoplastic transformation and tumor progression.
Highlights
Since their appearance in evolution, nature has evolved thousands of G protein coupled receptor (GPCR) isoforms to operate as cellular sensors in the most diversified organisms populating the earth.The variety of stimuli acting on GPCRs includes photons, lipids, peptides, amino acids, ions, etc
Other excellent candidates that could be targeted by antagonists, are GPCRs involved in embryonic signaling pathways that are crucial to preserve cancer stem cells (CSCs)
We recently described the differential sensitivity of G proteins of the Gq subfamily to -arrestin desensitization [72] and the same -arrestin emerged as versatile scaffold for important effectors upon sustained stimulation (Figure 1) [73]
Summary
Since their appearance in evolution, nature has evolved thousands of G protein coupled receptor (GPCR) isoforms to operate as cellular sensors in the most diversified organisms populating the earth. Progression and growth of prostate cancer cells require the production of testosterone via a signaling cascade that begins with the secretion of gonadotropin releasing-hormone (GnRH) from the hypothalamus. A pegylated peptide acting as GH antagonist licensed as a third or fourth line option when other treatments have failed to normalize IGF-1 levels. Both approaches described above act indirectly to inhibit cell growth or to prevent secondary effects caused by peptides released from the tumor. Abnormal expression of GPCRs and/or their ligands is directly observed in cancer cells of various origins that abuse GPCRs signaling to directly stimulate growth, induce angiogenesis, inhibit apoptosis, promote spreading and induce immune-tolerance [3,6] (Figure). In this review we describe the strategies that can be exploited to directly act on GPCRs to oppose neoplastic transformation and tumor progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
