Abstract 23P
Background
Adenoid Cystic Carcinoma (ACC) is a rare malignancy characterized by high incidence of relapse, with a poor long-term prognosis. The pharmacological approach is based on the combination of the chemotherapy drugs (cisplatin and doxorubicin); however, the response rate is low and not long-lasting. Alternative approaches for second-line therapies in case of disease progression are still lacking. In this study, the cytotoxic effects of both standard chemotherapy and targeted therapy drugs were evaluated, both in vitro and in vivo.
Methods
Cisplatin and doxorubicin as well as lenvatinib, vorinostat, everolimus, palbociclib and olaparib were tested alone or combined. The human ACC (hTERT) cell line, derived from a primary untreated ACC was used as experimental cell model. Cell viability was assessed by MTT assay, the cell proliferation was evaluated by cell counts. For in vivo evaluation, Danio rerio embryos were xenografted with ACC cells and exposed to the drugs for 3 days. The effect was evaluated by measuring the tumor areas.
Results
Cisplatin and doxorubicin reduced ACC cell viability and proliferation (over 90% efficacy). Vorinostat, olaparib, palbociclib and everolimus reduced the cell viability and proliferation, although with lower efficacy, except for vorinostat. Lenvatinib was scarcely effective and then excluded from subsequent evaluations. In the in vivo models, the drugs tested significantly reduced the tumor area. In the combination experiments, vorinostat + cisplatin or doxorubicin induced synergistic cytotoxic effects in ACC cells compare to single treatments. The combination of olaparib + cisplatin or doxorubicin resulted in an increased potency.
Conclusions
Vorinostat and olaparib significantly increased the standard chemotherapy cytotoxic effects, suggesting new interesting therapeutic options for ACC. These results on ACC, together with other high grade salivary gland cancers cell models, are now explored in depth as preclinical aim of the project granted by FRRB (ID3438215 - In depth analysis of salivary gland cancers: from cell lines and genomic evaluation towards clinical trials in locally advanced and recurrent/metastatic disease – INDAGA).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
University of Brescia (Local grant).
Disclosure
A. Berruti: Financial Interests, Personal, Invited Speaker: HRA; Financial Interests, Personal, Advisory Board: HRA; Financial Interests, Personal, Research Grant: Janssen, Sanofi, Novartis. P. Bossi: Financial Interests, Personal, Advisory Board: Merck, Sanofi-Regeneron, Sun Pharma, Angelini, Nestlé; Financial Interests, Institutional, Invited Speaker: MSD, GSK; Financial Interests, Personal, Invited Speaker: Merus, Pfizer, Elevar. All other authors have declared no conflicts of interest.