Our discovery from innovative laboratory research has led to the identification of R-roscovitine, a selective CDK inhibitor with dual effect suppressing both cell proliferation and ACTH production in pituitary corticotroph tumors. We now propose a pilot, proof of concept phase II clinical trial to treat with R-roscovitine of patiens with corticotroph tumors (Cushing disease), who are recruited from the Pituitary Center at Cedars-Sinai Medical Center, to determine if R-roscovitine can safely normalize urinary free cortisol levels by reducing pituitary corticotroph tumor ACTH production. R-roscovitine has been undergoing phase I and II clinical trials for several malignancies, and, if effective for corticotrph tumors, its oral dosing route and relatively mild side effects make daily long-term treatment of Cushing disease feasible. Our study will explore a novel intervention for much needed pharmaco-therapeutic strategies directly targeting pituitary corticotroph tumors, one of the most challenging human neuroendocrine diseases.

Public Health Relevance

We have identified a small molecule CDK2/cyclin E inhibitor, R-roscovitine, which has a dual action suppressing both cell proliferation and ACTH production in pituitary corticotroph tumors. By performing the proposed pilot, proof of concept phase II clinical trial with R-roscovitine, we will test a new and unique intervention directly targeting corticotroph tumors in patients with Cushing disease. Data collected from the proposed study will serve as a basis of developing a future R01 grant application for a full-scale clinical trial.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DK103198-01
Application #
8773516
Study Section
Special Emphasis Panel (ZRG1-EMNR-K (80))
Program Officer
Malozowski, Saul N
Project Start
2014-06-01
Project End
2016-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$234,382
Indirect Cost
$84,382
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
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