Biomedicine & Pharmacotherapy (Jan 2023)
The role and pharmacological properties of P2Y12 receptor in cancer and cancer pain
Abstract
The G protein-coupled P2Y12 receptor (P2Y12R) was cloned in platelets and found to play a key role in maintaining platelet function in hemostasis and thrombosis, and these effects could be mediated by the P2Y12R. However, it has recently been found that P2Y12R-mediated the progression of tumor through interactions between platelets and tumor and stromal cells, as well as through products secreted by platelets. During tumor progression, tumor cells or other cells in the tumor microenvironment (such as immune cells) can secrete large amounts of ATP into the extracellular matrix, and extracellular ATP can be hydrolyzed into ADP. ADP is a P2Y12R activator and plays an important regulatory role in the proliferation and metastasis of tumor cells. P2Y12R is involved in platelet-cancer cell crosstalk and become a potential target for anticancer therapy. Moreover, tumor progression can induce pain, which seriously affects the quality of life of patients. P2Y12R is expressed in microglia and mediates the activities of microglial and participates in the occurrence of cancer pain. Conversely, inhibiting P2Y12R activation and down-regulating its expression has the effect of inhibiting tumor progression and pain. Therefore, P2Y12R can be a common therapeutic target for both. In this article, we explored the potential link between P2Y12R and cancer, discussed the intrinsic link of P2Y12R in cancer pain and the pharmacological properties of P2Y12R antagonists in the treatment of both.
