Targeting histamine signaling: repurposing antihistamines for cancer chemotherapy and immunotherapy

Despite major advances in oncology, effective cancer treatment remains a major clinical challenge. Repurposing approved drugs offers a promising approach for developing novel therapies for various diseases, including cancer. Among key pathophysiological mediators, histamine and its receptors have emerged as important regulators of cancer cell growth, proliferation, metastasis, and drug resistance, presenting new opportunities for using antihistamines in cancer treatment. Histamine signals through four distinct types of receptors, H1R-H4R, each displaying mechanistic diversity; therefore, understanding the subtype-specific signaling of these receptors is important for interpreting their therapeutic relevance. This review examines the current evidence on how histamine and its receptors influence carcinogenesis, discussing the role of various histamine receptor antagonists in modulating oncogenic signaling pathways and the tumor microenvironment. This review highlights the potential role of antihistamines as adjuncts to existing cancer chemotherapies and immunotherapies.