Johns Hopkins Drug Discovery - Project - Chemotherapy-Induced Nausea and Vomiting
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Chemotherapy-Induced Nausea and Vomiting

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Biology work

Many patients undergoing moderately or highly emetogenic chemotherapy experience chemotherapy-induced nausea/vomiting (CINV) and report reduced daily functioning, despite prophylaxis with antiemetic drugs. While modern antiemetics have largely alleviated acute emesis, management of nausea and delayed emesis remains particularly challenging. Delayed emesis can be substantially reduced via combined 5-HT3 and NK1 receptor neurotransmitter pathway inhibition. One recently approved drug is a fixed-dose combination product, NEPA, which is composed of the NK1 receptor antagonist netupitant and the 5-HT3 receptor antagonist palonosetron(1). We are currently conducting studies aimed at elucidating the molecular mechanism of action of NEPA downstream of their respective antagonism(2, 3). These studies will provide an updated mechanistic description at the molecular level for NEPA’s efficacy in the clinic.

 

REFERENCES

1. Rojas C, Slusher BS. Mechanisms and latest clinical studies of new NK receptor antagonists for chemotherapy-induced nausea and vomiting: Rolapitant and NEPA (netupitant/palonosetron). Cancer Treat Rev. 2015 Sep 26. pii: S0305-7372(15)00169-3. [PubMed]

2. Stathis M, Pietra C, Rojas C, Slusher BS. Inhibition of substance P-mediated responses in NG108-15 cells by netupitant and palonosetron exhibit synergistic effects. Eur J Pharmacol. 2012;689(1-3):25-30. [PubMed]

3. Thomas AG, Stathis M, Rojas C, Slusher BS. Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells. Exp Brain Res. 2014;232(8):2637-44. [PubMed]