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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011286-04
Application #
8763433
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2013
Total Cost
$1,233,547
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
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Nilubol, Naris; Yuan, ZiQiang; Paciotti, Giulio F et al. (2018) Novel Dual-Action Targeted Nanomedicine in Mice With Metastatic Thyroid Cancer and Pancreatic Neuroendocrine Tumors. J Natl Cancer Inst :
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Luo, Hongxiu; Tobey, Andrew; Auh, Sungyoung et al. (2018) The effect of lithium on the progression-free and overall survival in patients with metastatic differentiated thyroid cancer undergoing radioactive iodine therapy. Clin Endocrinol (Oxf) 89:481-488
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Kebebew, Electron (2018) Thyroid Cancer: Is It All in the Genes? J Natl Cancer Inst 110:327-328
Tirosh, Amit; El Lakis, Mustapha; Green, Patience et al. (2018) In silico VHL Gene Mutation Analysis and Prognosis of Pancreatic Neuroendocrine Tumors in von Hippel-Lindau Disease. J Clin Endocrinol Metab 103:1631-1638
El Lakis, Mustapha; Nockel, Pavel; Guan, Bin et al. (2018) Familial isolated primary hyperparathyroidism associated with germline GCM2 mutations is more aggressive and has a lesser rate of biochemical cure. Surgery 163:31-34
Nockel, Pavel; El Lakis, Mustapha; Gaitanidis, Apostolos et al. (2018) Preoperative genetic testing in pheochromocytomas and paragangliomas influences the surgical approach and the extent of adrenal surgery. Surgery 163:191-196

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