(Top). Representative protumorigenic GPCRs can regulate cancer at multiple levels, including immune cell recruitment to TME, angiogenesis, and tumor biology. (Bottom). Multiple and parallel targeting of selected protumorigenic GPCRs might overcome receptor redundancy and impede tumor growth on various fronts, thus increasing the therapeutic potential of GPCR-targeted therapies.
Abstract
G protein-coupled receptors (GPCRs) are vital cell surface receptors that govern a myriad of physiological functions. Despite their crucial role in regulating antitumor immunity and tumorigenesis, therapeutic applications targeting GPCRs in oncology are currently limited. This review offers a focused examination of selected protumorigenic chemokine and metabolite-sensing GPCRs. Specifically, the review highlights five GPCRs able to orchestrate tumor immunobiology at three main levels: tumor immunity, cancer cell expansion, and blood vessel development. The review culminates by illuminating emerging therapies and discussing innovative strategies to harness the full potential of GPCR-targeted treatments, by applying a multireceptor and patient-specific logic.