Mortality-to-incidence ratio in
cancer patients is extremely high, positioning
cancer as a major cause of death worldwide. Despite hundreds of clinical trials for anti-
cancer drugs that are currently in progress, most clinical trials for novel
drug treatments fail to pass Phase I. However, previously developed drugs with novel anti-
tumor properties offer a viable and cost-effective alternative to fight
cancer.
Histamine favors the proliferation of normal and malignant cells. Several anti-
histamine drugs, including
astemizole, can inhibit
tumor cell proliferation.
Astemizole has gained enormous interest since it also targets important
proteins involved in
cancer progression, namely,
ether à-go-go 1 (Eag1) and Eag-related gene (
Erg) potassium channels. Furthermore, Eag1 is thought to be an important marker and a therapeutic target for several different
cancers.
Astemizole inhibits Eag1 and Erg channel activity, and in cells expressing the Eag1 channel it decreases
tumor cell proliferation in vitro and in vivo. It should be noted that some cardiovascular side effects have been reported for
astemizole in a few rare cases. Nevertheless,
astemizole stands as a very promising anti-
cancer tool because it displays several anti-proliferative mechanisms, may serve as the basis to synthesize new anti-
cancer agents, and has been previously administered clinically. In this review we will summarize the main findings relating to
histamine and anti-histamines in
cancer cell proliferation focusing on
astemizole targets (Eag1 and Erg channels), and its anti-
cancer effects in vitro and in vivo. We will also describe the side effects of
astemizole and discuss proposals to overcome such effects in
cancer patients. Finally, we will remark on the relevance of developing novel
astemizole-related compounds.