Histamine receptors in cancer

VANINA A MEDINA

Congreso; European Histamine Research Society 46th Annual Meeting. 11 al 13 de Mayo de 2017. Amsterdam, Holanda.; 2017

Cancer is one of the leading causes of morbidity and mortality worldwide. Substantial evidence demonstrates that histamine modulates biological responses related to tumor progression with different effects depending on the histamine receptor subtype involved and the cell type. Expression of histamine H4 receptors (H4R) has been described in different tumor subtypes, with these receptors playing a key role in histamine-mediated effects. Thus, histamine and H4R agonists reportedly inhibit proliferation of human breast cancer and melanoma cells in vitro and in vivo, augmenting cell death, differentiation and senescence. Chemotherapy and radiotherapy are major treatments of medical oncology. However, their related toxicities frequently outweigh their clinical benefits and worsen a patient's quality of life.In this regard, histamine increases the antitumor efficacy of a chemotherapeutic agent or ionizing radiation in experimental models of human breast cancer and melanoma developed in immunodeficient mice, by modulating DNA damage, oxidative stress and cell death.Recent studies in murine breast cancer developed in immunocompetent mice allowed an examination of the effect of histamine not only on metastatic potential, but also on the immune system and inflammatory processes, since these latter processes play a fundamental role in regulating tumor development and progression. Modulation of tumor immunity was found to be involved in the effects of histamine on tumor development.The latest evidence regarding the involvement of histamine and H4R in breast cancer and melanoma was discussed in my presentation. The findings presented support exploitation of the H4R as a molecular target for cancer drug development.