Fighting Cancer Using Selective Antagonists Targeting the Substance P/Neurokinin-1 Receptor System
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Coveñas, Rafael
14
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Rodríguez, Francisco D.
34
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Muñoz, Miguel
2
- 1 Laboratory of Neuroanatomy of the Peptidergic Systems, Institute of Neurosciences of Castilla y León (INCYL), University of Salamanca, Salamanca, Spain
- 2 Research Laboratory on Neuropeptides, Institute of Biomedicine (IBIS), University of Sevilla, Sevilla, Spain
- 3 Department of Biochemistry and Molecular Biology, Faculty of Chemical Sciences, University of Salamanca, Salamanca, Spain
- 4 Group GIR-BMD (Bases Moleculares del Desarrollo), University of Salamanca, Salamanca, Spain
ISSN: 2731-4561, 2731-457X
Year of publication: 2024
Type: Book chapter
Abstract
Peptidergic systems are closely associated with cancer development by promoting cell proliferation and migration. Cancer cells generally overexpress peptide receptors (PRs) in comparison with normal cells. One of the most studied peptidergic systems in this context is the substance P (SP)/neurokinin-1 receptor (NK-1R) complex. Preclinical research supports that NK-1R antagonists favor apoptotic mechanisms in tumor cells.SP promotes the development of different cancers; hence, a common antitumor approach using NK-1R antagonists appears feasible. SP favors the growth and dissemination of malignant cells, angiogenesis, and the Warburg effect and exhibits an antiapoptotic action. Cancer cells overexpress NK-1R, which is essential to support tumor cells’ survival. However, the expression of SP is not involved in their viability. NK-1R overexpression may be a reliable tumor biomarker. The selective NK-1R antagonist aprepitant experimentally induces the apoptosis of malignant cells and exhibits a broad-spectrum antitumor activity against many types of cancer. Remarkably, it could serve to fight tumors without considering their biology and clinical stage.Repurposing aprepitant as an antitumor agent is a crucial scientific challenge that must be urgently considered to treat cancer patients alone or combined with chemotherapy or radiotherapy. This repurposing will offer a new focus on clinical applications in oncology. Clinical trials (phases I and II) defining doses are imperiously required to check the efficacy, pharmacokinetics, tolerability, and safety of high doses of aprepitant. This chapter aims to show that NK-1R is a promising antitumor target.
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