Treatment of parathyroid neoplasia by pharmacologic cdk4/6 inhibition

通过药物抑制 cdk4/6 治疗甲状旁腺肿瘤

• 批准号: 10372170
• 负责人: Jessica Costa
• 金额: $ 8.2万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10372170
• 关键词: Adjuvant; Antineoplastic Agents; Binding; Biochemical; Biological Models; CCND1 gene; CDK4 gene; Complex; Cyclin D1; Disease; Disease of parathyroid glands; Effectiveness; Excision; G1 Phase; Gene Mutation; Growth; Hormonal; Hypercalcemia; Hyperparathyroidism; Intervention; Kinetics; Life; Malignant Neoplasms; Mammary Tumorigenesis; Mediating; Medical; Metabolic; Molecular Abnormality; Molecular Genetics; Morbidity - disease rate; Neck; Neoplasms; Operative Surgical Procedures; PTH gene; Parathyroid Gland Adenocarcinoma; Parathyroid Neoplasms; Parathyroid gland; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacology; Phosphorylation; Phosphotransferases; Pre-Clinical Model; Primary Neoplasm; Radiation; Recurrence; Research; Retinoblastoma Protein; S phase; Support System; Testing; Tissues; Transgenes; Transgenic Mice; Tumor Burden; Tumor Suppressor Genes; cancer type; cell growth; cinacalcet; high risk; improved outcome; inhibitor; inhibitor therapy; malignant parathyroid gland tumor; mortality; mouse model; mutant; neoplastic cell; overexpression; precision medicine; preclinical study; research study; therapeutic target; tumor; tumorigenic

Project Summary: 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.

项目概要： 甲状旁腺癌是一种罕见但通常无法治愈的恶性肿瘤。甲状旁腺激素长期升高 以及伴随的高钙血症导致显著的发病率和死亡率。手术仍然是主要的 在约50%的患者中观察到治疗和复发。精准医学方法可以改善结果 手术无法治愈的病人药理学cdk 4/6抑制剂最近已被 用于治疗各种类型的癌症，结果好坏参半。这些药物可能对 30%的甲状旁腺癌具有细胞周期蛋白D1扩增。本研究的目的是评估 药理学cdk 4/6抑制剂在细胞周期蛋白D1驱动的小鼠甲状旁腺肿瘤模型中的作用。转基因 将用CDK 4/6抑制剂Palbociclib或abemaciclib单独或与 西那卡塞这些临床前研究将有助于确定药物cdk 4/6抑制剂是否可能被用于治疗癌症。 在肿瘤含有细胞周期蛋白D1扩增/重排的甲状旁腺癌患者中有效， 可能建立一种新的治疗方法，用于治疗无法治愈的甲状旁腺癌患者。