Some Antihistamines Found to Treat Cancer

Researcher Aims to Hinder Allergic Responses, Keep Cancer Cells from Dividing
Dr. Glenn Cruse, an associate professor of immunology at the NC State College of Veterinary Medicine, researches "the molecular mechanisms — including genes and proteins — that control mast cell function, with the hope of developing ways to prevent mast cells from being activated. His research also aims to develop therapeutics for cancer by inhibiting the KIT growth factor receptor in mast cells."  His team is currently studying "the MS4A gene family that have been associated with asthma susceptibility."  His team has already found a way to induce the cell to make a defective version of a subunit of the receptor, called MS4A2, which doesn't trigger the inflammatory response when IgE is bound to it.  These findings show potential for becoming a treatment for asthma, but the team also discovered that in humans there is another, related protein that partially compensates for the defective one, meaning a treatment in humans must be more complex.

"We previously found an exon-skipping oligonucleotide, which we have termed KitStop, that safely reduces the severity and duration of the anaphylactic response by depopulating mast cells in tissues. We target a growth factor receptor called KIT that’s critical for mast cell survival and force it to produce a different version of that mRNA code for a protein. By doing that, we make the protein and growth factor receptor nonfunctional, essentially causing mast cells to die." This might prove to be an effective treatment for mast cell cancers and mast cell leukemia, as well as forms of mastocytosis that involve invasion of the tissues by mast cells, by being able to selectively kill the mast cells. 

Desloratadine and loratadine stand out among common H1-antihistamines for association with improved breast cancer survival
"As tumors maintain an inflammatory microenvironment, anti-inflammatory medication can be useful in cancer therapy. We have previously shown an association with improved survival in melanoma for use of the H₁-antihistamines desloratadine and loratadine, and here we examine use of H₁-antihistamines and breast cancer mortality.  We investigated use of the six major H₁-antihistamines (cetirizine, clemastine, desloratadine, ebastine, fexofenadine and loratadine) and breast cancer-specific and overall mortality in a nation-wide register-based study of all 61,627 Swedish women diagnosed with breast cancer 2006–2013.  

We found a consistently improved survival of desloratadine users, as well as of loratadine users, relative to nonusers, regardless of patient age, menopause, estrogen receptor status or stage of the tumor, or whether breast cancer-specific or overall survival was analyzed. The survival of users of other antihistamines varied relative to non-users.

Based on their safety and current use within the patient population, together with our observations, we suggest the initiation of trials of desloratadine and loratadine as treatment of breast cancer as well as studies of the mechanism behind their possible effect. Further studies on any effects of other H₁-antihistamines may also be merited, as well as of H₁-antihistamine use and survival in other malignancies."

Histamine receptor 1 inhibition enhances antitumor therapeutic responses through extracellular signal-regulated kinase (ERK) activation in breast cancer

Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment
"Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide. In search for new NSCLC treatment options, we screened a cationic amphiphilic drug (CAD) library for cytotoxicity against NSCLC cells and identified several CAD antihistamines as inducers of lysosomal cell death. We then performed a cohort study on the effect of CAD antihistamine use on mortality of patients diagnosed with non-localized cancer in Denmark between 1995 and 2011. The use of the most commonly prescribed CAD antihistamine, loratadine, was associated with significantly reduced all-cause mortality among patients with non-localized NSCLC or any non-localized cancer when compared with use of non-CAD antihistamines and adjusted for potential confounders. Of the less frequently described CAD antihistamines, astemizole showed a similar significant association with reduced mortality as loratadine among patients with any non-localized cancer, and ebastine use showed a similar tendency."

H1-Antihistamines Reduce the Risk of Hepatocellular Carcinoma in Patients With Hepatitis B Virus, Hepatitis C Virus, or Dual Hepatitis B Virus-Hepatitis C Virus Infection
"AH use may reduce the risk for HCC among patients with HBV, HCV, or dual infection in a dose-dependent manner. Further mechanistic research is needed."