INTRODUCTION
The natural history of adenoid cystic carcinoma (ACC) is relentless, defined by treatment failure, locoregional recurrence and metastatic disease. Treatment options are limited to palliative systemic therapy. Despite the introduction of therapies against new treatment targets, clinical trials present poor response rates and survival benefit.
METHODS
Our research is focused on improving the therapeutic potential for treatment targets in head and neck ACC. This work has focused on the application of novel prochlorperazine (PCZ) combination therapy to promote increased clustering of treatment targets. This repurposing of PCZ is centred on inhibition of dynamin mediated endocytosis pathways. The combination therapy of PCZ and cetuximab (anti-EGFR) combination therapy has recently completed phase I clinical trials and is soon to commence phase II trial. Our research is now centred on the application of PCZ combination therapy to ACC treatment targets, including prostate specific membrane antigen (PSMA). PSMA is expressed in up to 94% of ACC cases and is internalised via the same mechanisms as EGFR opening the possibility of PCZ combination therapy to promote tumour homogeneity and improved treatment responses.
RESULTS
We present application of PSMA from its namesake in the prostate to head and neck ACC. This includes PCZ spatiotemporal manipulation across preclinical models in PSMA expressing disease. This translational research is centred on improved PET staging, radionuclide and immunotherapy applications. This is underpinned by presented clinicopathological data and correlated treatment targets highlighting an ACC patient population in need for improved treatment.
CONCLUSION
This presentation presents the foundation for improving response rates and outcomes for therapeutics undergoing clinical trial and future immunotherapy applications in ACC and PSMA expressing cancers.