Abstract A106: Utilization of low passage adenoid cystic carcinoma (ACC) models to identify novel therapies.

Abstract

Abstract Background: Adenoid Cystic Carcinoma (ACC) is an uncommon cancer of the head and neck which typically originates in the salivary glands. Treatment options for ACC resection and local radiation therapy although chemotherapy is sometimes used to control metastatic or locally recurrent disease. Patients with ACC may survive for years due to latent tumor growth and lack of lymph node metastasis; however, the high rate of recurrence and metastasis to the lungs lead to a poor prognosis beyond ten years. While no standard of care currently exists, improved understanding of ACC tumor biology and oncogenesis has provided some molecular targets for its treatment. Mutations and alterations of MYB, NFIB and molecules in the FGF, IGF, PI3K and NOTCH signaling pathways amongst others, may serve as targets for current and future therapies. Due to a lack of ACC derived cell lines, a panel of low passage ACC xenograft models designated ACCx5M1, ACCx6, ACCx9, ACCx14 and ACCx16 have been established and through the Adenoid Cystic Carcinoma Research Foundation (ACCRF) are routinely utilized to test agents which target pathways important in ACC. Methods: Low passage ACC models were established in immune-deficient mice from primary or metastatic patient tissue and once established were confirmed by histologic comparative analysis. Drug sensitivity studies are performed evaluating models towards chemotherapy and targeted agents. Study endpoints included tumor volume and time from treatment initiation with tumor growth inhibition and regression reported at study completion. Results: To date over seventy FDA-approved and investigational therapies have been evaluated and data has been generated that have contributed to the initiation of two Phase 2 clinical trials in ACC. In addition to chemotherapies, therapies targeting FGF, IGF, VEGF and NOTCH pathways have been tested and we are currently evaluating agents targeting MYB dysregulation. Conclusion: Low passage ACC models have been used to identify agents potentially useful in the treatment of ACC and models are available through the ACCRF to evaluate potential therapies for the treatment of adenoid cystic carcinoma. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A106. Citation Format: Justin Meade, Michael J. Wick, Teresa L. Vaught, Jennifer Carlile, Anthony W. Tolcher, Drew Rasco, Amita Patnaik, Jeffrey Kaufman, Chris Moskaluk, Kyriakos P. Papadopoulos. Utilization of low passage adenoid cystic carcinoma (ACC) models to identify novel therapies. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A106.