3 years ago

Histamine Receptors and Cancer Pharmacology: An Update

Noelia A Massari, Melisa B Nicoud, Vanina A Medina

Abstract

In the present review we will discuss the recent advances in the understanding of the role of histamine and histamine receptors in cancer biology. The controversial role of the histaminergic system in different neoplasias including gastric, colorectal, oesophageal, oral, pancreatic, liver, lung, skin, blood and breast cancers will be reviewed. The expression of histamine receptor subtypes, with special emphasis in histamine H4 receptor (H4R), in different cell lines and human tumours, the signal transduction pathways and the associated biological responses as well as the in vivo treatment of experimental tumours with pharmacological ligands will be described. The presented evidence demonstrates that histamine regulates cancer‐associated biological processes during cancer development in multiple cell types, including neoplastic cells and cells of tumour microenvironment. The outcome will depend on tumour cell type, histamine receptors expression, signal transduction associated to those receptors, tumour microenvironment and histamine metabolism, supporting the complexity of cancer disease. Findings show the pivotal role of H4R in the development and progression of many types of cancers, and considering its immunomodulatory properties, H4R arises as the most promising molecular therapeutic target for cancer treatment within histamine receptor family. Furthermore, H4R is differentially expressed in tumours compared with normal tissues and in most cancer types in which data was available, H4R expression is associated to clinicopathological characteristics, suggesting that H4R might represent a novel cancer biomarker.

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