Frontiers in Anti-Cancer Drug Discovery

Volume: 4

Indexed in: Scopus, EMBASE, EBSCO, Ulrich's Periodicals Directory.

Frontiers in Anti-Cancer Drug Discovery is an Ebook series devoted to publishing the latest and the most important advances in Anti-Cancer drug design and discovery. Eminent scientists write ...
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Substance P, the NK-1 Receptor and NK-1 Receptor Antagonists in Cancer Treatment

Pp. 3-38 (36)

Miguel Muñoz and Rafael Coveñas

Abstract

Despite the great efforts made in research into cancer, in the last two decades therapeutic progress has unfortunately been very limited. It is crucial to seek new avenues of enquiry able to provide solutions to this scientific challenge. Currently, the term “Magic Bullet”, coined by Paul Ehrlich, should be revisited and applied to new, more selective and effective cancer treatments. The peptide substance P (SP) exerts an important role in cancer progression. After the binding of SP to the tachykinin neurokinin-1 receptor (NK-1 receptor), the peptide exerts a mitogenic action on tumour and endothelial cells (inducing angiogenesis). It also regulates the migration of tumour cells and exerts an antiapoptotic effect on them. However, when NK-1 receptor antagonists bind to NK-1 receptors, these antagonists block the functions regulated by SP. These antagonists inhibit tumour cell proliferation (tumour cells die by apoptosis), angiogenesis, and tumour cell migration. These antagonists are broad-spectrum antitumour drugs. It is known that the administration of NK-1 receptor antagonists in combination with cytostatics exerts a synergic effect and decreases the side effects induced by cytostatics to a considerable extent. Many authors have suggested that these antagonists should be called “Intelligent Bullets”, because cancer cells overexpress the NK-1 receptor and hence NK-1 receptor antagonists could act as specific anticancer drugs. The aim of the present study is to update knowledge of the involvement of the SP/NK-1 receptor system in cancer progression. We also suggest the use of NK-1 receptor antagonists as an anticancer therapy.

Keywords:

Antitumour, aprepitant, cancer, metastasis, mitogenesis, neoangiogenesis, NK-1 receptor antagonists, substance P, tachykinin NK-1 receptor.

Affiliation:

Research Laboratory on Neuropeptides (IBIS), Virgen del Rocío University Hospital, Pediatric Intensive Care Unit, Av. Manuel Siurot s/n, 41013 - Sevilla, Spain.