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Review

The Neurokinin-1 Receptor Antagonist Aprepitant, a New Drug for the Treatment of Hematological Malignancies: Focus on Acute Myeloid Leukemia

1
Research Laboratory on Neuropeptides (IBIS), Virgen del Rocío University Hospital, 41013 Sevilla, Spain
2
Institute of Neurosciences of Castilla y León (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems, University of Salamanca, 37007 Salamanca, Spain
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(6), 1659; https://doi.org/10.3390/jcm9061659
Received: 13 April 2020 / Revised: 9 May 2020 / Accepted: 28 May 2020 / Published: 1 June 2020
(This article belongs to the Special Issue Advances in Acute Myeloid Leukemia)
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy. To treat the disease successfully, new therapeutic strategies are urgently needed. One of these strategies can be the use of neurokinin-1 receptor (NK-1R) antagonists (e.g., aprepitant), because the substance P (SP)/NK-1R system is involved in cancer progression, including AML. AML patients show an up-regulation of the NK-1R mRNA expression; human AML cell lines show immunoreactivity for both SP and the NK-1R (it is overexpressed: the truncated isoform is more expressed than the full-length form) and, via this receptor, SP and NK-1R antagonists (aprepitant, in a concentration-dependent manner) respectively exert a proliferative action or an antileukemic effect (apoptotic mechanisms are triggered by promoting oxidative stress via mitochondrial Ca++ overload). Aprepitant inhibits the formation of AML cell colonies and, in combination with chemotherapeutic drugs, is more effective in inducing cytotoxic effects and AML cell growth blockade. NK-1R antagonists also exert an antinociceptive effect in myeloid leukemia-induced bone pain. The antitumor effect of aprepitant is diminished when the NF-κB pathway is overactivated and the damage induced by aprepitant in cancer cells is higher than that exerted in non-cancer cells. Thus, the SP/NK-1R system is involved in AML, and aprepitant is a promising antitumor strategy against this hematological malignancy. In this review, the involvement of this system in solid and non-solid tumors (in particular in AML) is updated and the use of aprepitant as an anti-leukemic strategy for the treatment of AML is also mentioned (a dose of aprepitant (>20 mg/kg/day) for a period of time according to the response to treatment is suggested). Aprepitant is currently used in clinical practice as an anti-nausea medication. View Full-Text
Keywords: substance P; NK-1R; AML; aprepitant; anti-leukemic; apoptosis; non-solid tumor substance P; NK-1R; AML; aprepitant; anti-leukemic; apoptosis; non-solid tumor
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MDPI and ACS Style

Muñoz, M.; Coveñas, R. The Neurokinin-1 Receptor Antagonist Aprepitant, a New Drug for the Treatment of Hematological Malignancies: Focus on Acute Myeloid Leukemia. J. Clin. Med. 2020, 9, 1659. https://doi.org/10.3390/jcm9061659

AMA Style

Muñoz M, Coveñas R. The Neurokinin-1 Receptor Antagonist Aprepitant, a New Drug for the Treatment of Hematological Malignancies: Focus on Acute Myeloid Leukemia. Journal of Clinical Medicine. 2020; 9(6):1659. https://doi.org/10.3390/jcm9061659

Chicago/Turabian Style

Muñoz, Miguel, and Rafael Coveñas. 2020. "The Neurokinin-1 Receptor Antagonist Aprepitant, a New Drug for the Treatment of Hematological Malignancies: Focus on Acute Myeloid Leukemia" Journal of Clinical Medicine 9, no. 6: 1659. https://doi.org/10.3390/jcm9061659

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