Background: Thyroid cancer: The incidence of thyroid cancer has doubled over the last two decades. Although most patients with thyroid cancer of follicular cell origin have an excellent prognosis, 10% - 15% will have refractory disease to conventional therapy (resection combined with radioiodine ablation and thyroid hormone for TSH suppression). Chemotherapy and external beam radiation are ineffective in patients with metastatic disease. The overall 10 year survival of patients with metastatic thyroid cancer of follicular cell origin is approximately 40-50%. Adrenocortical carcinoma: Approximately two-thirds of patients who present with adrenocortical carcinoma have locoregional disease and metastasis. Unfortunately, despite combined multimodality therapy, the overall prognosis of patients with adrenocortical carcinoma remains dismal, with a 5-year survival of less than 35%. Summary: We have made progress towards identifying molecular targets and novel agents for endocrine cancer therapy. From our pangenomic studies of endocrine cancers (thyroid and adrenal), we have identified altered genes/pathways which are druggable targets. By integrating this data with quantitative high throughput screening of over 3,000 compounds, which showed anticancer activity in thyroid and adrenal cell lines, we have identified compounds uniformly effective across all cancer cell lines studied and with different driver mutations. We are currently validating the activities of these compounds in vivo as well as performing matrix drug screening of compounds with established standard of care drugs for combination therapy evaluation. Based on this work we are also currently developing two clinical protocols for anaplastic thyroid cancer and adrenal cancer.
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