Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Despite aggressive multimodal management, a significant proportion of patients with head and neck squamous cell carcinomas (HNSCC) experience locoregional or distant failure highlighting the need to develop innovative treatment strategies for this patient population. In this context, repurposing existing clinically approved drugs is a cost-effective and time-efficient strategy that could enable identification of agents that could exhibit potent anticancer activity against HNSCC. Using this approach, we have recently conducted a high throughout drug screening of over 1500 compounds in patient-derived organoid models of HNSCC. These studies led us to identify Penfluridol (Pen), an FDA approved antipsychotic drug, as a potential candidate for further development. In the present study, we evaluated the therapeutic efficacy and mechanistic effects of Pen using in vitro and in vivo experimental models of HNSCC. In vitro studies using RP-MOC1 and SCCVII cell lines revealed half-maximal inhibitory concentration (IC50) of Pen to range from 3-9 μM. Treatment of RP-MOC1 cells in culture reduced phosphorylated ERK expression and induced cleaved caspase-3 expression. Experimental studies conducted in vivo revealed tumor growth inhibition with Pen (10 mg/kg, QD, i.p.) monotherapy in the RP-MOC1 model but not SCCVII. However, the combination of Pen with cisplatin (2 mg/kg, QOD x 3, i.p.) results in tumor growth inhibition in both models without any evidence of toxicity. Collectively, these results highlight the potential of Pen as a novel agent for potential therapeutic development against HNSCC.