The Role of Tachykinins in the Initiation and Progression of Gastrointestinal Cancers: A Review

Context: Tachykinins (TKs), an evolutionarily conserved family of peptide hormones, are widely distributed within the peripheral and central nervous systems. TKs exert their biological actions in many processes via three subtypes of transmembrane G-protein coupled receptors, which are NK1R, NK2R, and NK3R. Although the mechanisms that connect TKs peptide activity to physiological processes are currently precise, it has been shown that TKs over-activation is associated with the pathogenesis of many diseases, including pain, emesis, depression, stress, and inflammatory processes, as well as human tumors. Gastrointestinal (GI) cancers refer to malignant conditions of the GI tract, which are among the most prevalent diseases and are the leading cause of cancerrelated death worldwide. Recent studies have shown that the binding of TKs to specific cellular receptors mediates a critical GI tumor proliferation pathway via initiation and activation of effector mechanisms, including protein synthesis and progression of the eukaryotic cell cycle. Evidence Acquisition: This study reviewed the role of tachykinins in the initiation and progression of gastrointestinal cancers. In this regard we searched databases such as PubMed, Science Direct, Google Scholar, and Scopus databases by using these keywords Tachykinins, Gastrointestinal cancer, Metastasis, G-protein coupled receptors, and pharmacological inhibitor without any time limit. The relevance of studies was identified by reviewing the titles and the abstracts. A total of 100 English language articles including experimental, observational, molecular, and cellular studies were reviewed. Results: The administration of the gastrointestinal cancer cells with Tk receptor antagonists induces apoptotic cell death through the tachykinin-mediated pathway. The findings showed that the pharmacological inhibition of TKRs with its selective antagonists has a promising prospect for the GI cancers treatment approach, either as a single agent or in combination with other chemotherapeutic agents. Conclusions: In this review, we presented different facts regarding the role of TKs and TKRs in the pathogenesis of GI malignancies for a better understanding and hence better management of these cancers. Therefore, understanding the underlying mechanism of the TK/TKR system can help to have a more excellent clinical vision for the treatment of GI cancers.