Abstract 2887: Evaluating the effectiveness of MAPK, AKT, and mTOR inhibitors in reducing proliferation in cellular models of papillary and follicular thyroid cancer

Abstract

Abstract Thyroid cancer is the most common endocrine malignancy, and incidence has been steadily increasing, suggesting occurrence will exceed that of colon cancer by 2030. Papillary and follicular thyroid cancer subtypes are most common, which are activated by BRAF and HRAS mutations, respectively. Interestingly, papillary and follicular thyroid cancers are associated with different pathologies and metastases. Currently, both papillary and follicular thyroid cancers are treated by surgical removal of the thyroid, followed by radioactive iodine treatment to eliminate any remaining tumor cells. Unfortunately, for individuals with progressive thyroid cancer, these treatment options are not effective, highlighting a need for increased investigation into mechanisms of drug sensitivity. In this study, we sought to evaluate mechanisms of differential drug sensitivity through RNA-seq analysis of cell lines derived from mouse models of papillary and follicular thyroid cancer. Additionally, we evaluated the effects of MAPK, AKT, and mTOR inhibitors on murine papillary and follicular thyroid cancer cell proliferation. To accurately assess drug efficacy, we calculated GR50 concentrations for each inhibitor in six papillary and follicular thyroid cancer cell lines. We discovered that papillary and follicular thyroid cancer cell lines responded differently to MAPK and AKT inhibitors, suggesting that treatment approaches should be tailored to subtype despite having mutations in the same signaling pathway. Citation Format: Brianna LeBoeuf, Braxton Anderson, Margaret Young, Aime Franco, Laura MacDonald. Evaluating the effectiveness of MAPK, AKT, and mTOR inhibitors in reducing proliferation in cellular models of papillary and follicular thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2887.