Parathyroid cancer is a rare, but typically incurable malignancy. Prolonged elevation of parathyroid hormone and accompanying hypercalcemia cause significant morbidity and mortality. Surgery remains the primary treatment and recurrence is seen in ~50% of patients. A precision medicine approach may improve outcomes for patients whose disease is surgically incurable. Pharmacologic cdk4/6 inhibitors have recently been introduced for the treatment of various cancer types, with mixed results. These drugs might be effective in the 30% of parathyroid cancers which harbor cyclin D1 amplification.
The aim of this study is to assess the efficacy of pharmacologic cdk4/6 inhibitors in a cyclin D1-driven mouse model of parathyroid neoplasia. Transgenic mice will be treated with the cdk4/6 inhibitors palbociclib or abemaciclib, alone or in combination with cinacalcet. These pre-clinical studies will help to determine if pharmacologic cdk4/6 inhibitors are likely to be effective in parathyroid carcinoma patients whose tumors harbor amplifications/rearrangements of cyclin D1, potentially establishing a new treatment for patients with surgically-incurable parathyroid cancer.

Public Health Relevance

This research will examine the effectiveness of a new class of cancer drugs, known as cdk4/6 inhibitors, in a mouse model of parathyroid tumors. This research will help us determine if these drugs are likely to be effective in certain patients with parathyroid cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA259649-01
Application #
10200999
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
O'Hayre, Morgan
Project Start
2021-03-15
Project End
2023-02-28
Budget Start
2021-03-15
Budget End
2022-02-28
Support Year
1
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Dentistry
Type
Schools of Dentistry/Oral Hygn
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
06030