Chemoprevention of basal cell carcinoma with vitamin D

描述（由申请人提供）：这是加州大学弗朗西斯科分校皮肤科医生Jean Tang博士的K23奖申请。Tang博士是一名年轻的研究者，致力于以患者为导向的基底细胞癌（BCC）预防转化研究。该K23奖项将为Tang博士提供必要的支持，以实现以下目标：（1）进行维生素D预防BCC的小鼠临床前试验;（2）在具有基线维生素D测量值的大型前瞻性老年男性队列中进行二次数据分析;（3）进行人体试点临床试验，以测试局部或口服维生素D3的可行性。为了实现这些目标，Tang博士组建了一个指导团队，由主要导师Ervin Epstein博士（奥克兰研究所儿童医院科学家）和三位共同导师组成：Steven Cummings博士，弗朗西斯科协调中心主任，他是大型患者队列临床研究和试验专家; Mary-Margaret Chren博士，皮肤病学成果研究专家; Charles McCullough博士，在纵向数据分析和生物统计学方面具有专业知识。目前，没有有效的药物来预防基底细胞癌（BCC）。防晒霜还没有被证明可以预防BCC;然而，最近的体外数据表明，维生素D3抑制BCC中发现的异常信号通路。唐博士已经表明，在小鼠中局部应用维生素D3可以预防50%的BCC。在这个K23中，她建议确定维生素D3抑制小鼠BCC的最佳途径（目标1），并确定高水平的血清维生素D是否会降低老年人BCC的风险（目标2）。Tang博士还将进行一项试点临床试验，以测试局部和口服维生素D3在患有多个BCC的基底细胞痣综合征患者中的可行性（Aim 3）。通过小鼠临床前试验和人体中试试验，我们将确定维生素C的最佳给药方案。 D3用于抑制BCC的生物标志物。这些结果将为使用维生素D3预防基底细胞痣综合征患者BCC肿瘤的随机对照临床试验提供关键的初步数据，该试验将在K奖期间开发，并在年底作为R34资助申请提交给NIH第5年。相关性（见说明）：防晒霜不能预防皮肤基底细胞癌，这是美国最常见的癌症。我们的目标是确定维生素D是否是预防基底细胞癌的有效和安全的药物。

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Jean Tang, a dermatologist at the University of California, San Francisco. Dr. Tang is establishing herself as a young investigator in patient-oriented, translational research in the prevention of basal cell carcinoma (BCC). This K23 award will provide Dr. Tang with the support necessary to accomplish the following goals: (1) to conduct a mouse preclinical trial on vitamin D for BCC prevention; (2) to conduct secondary data analysis in a large prospective cohort of senior men that have baseline vitamin D measurements; (3) to conduct a pilot clinical trial in humans to test the feasibility of topical or oral vitamin D3. To achieve these goals, Dr. Tang has assembled a mentoring team comprised of a primary mentor, Dr. Ervin Epstein, Scientist at Children's Hospital of Oakland Research Institute, who conducts laboratory and clinical trials in chemoprevention of BCC, and three co-mentors: Dr. Steven Cummings, Director of the San Francisco Coordinating Center who is an expert in clinical studies and trials of large patient cohorts; Dr. Mary-Margaret Chren, an expert in dermatology outcomes research; and Dr. Charles McCullough, who has expertise in longitudinal data analysis and biostatistics. Currently, there is no effective agent to prevent basal cell carcinomas (BCC). Sunscreens have not been shown to prevent BCC; however, recent in vitro data suggests that vitamin D3 inhibits the aberrant signaling pathway found in BCC. Dr. Tang has shown that topical application of vitamin D3 in mice will prevent 50% of BCCs. In this K23, she proposes to determine the optimal route of delivery of vitamin D3 for inhibition of BCC in mice (Aim 1) and to determine whether high levels of serum vitamin D reduce BCC risk in senior men (Aim 2). Dr. Tang will also conduct a pilot clinical trial to test the feasibility of topical and oral vitamin D3 in patients with basal cell nevus syndrome who have multiple BCCs (Aim 3). From the mouse preclinical trial and the human pilot trial, we will determine the optimal administration of vitamin D3 for inhibition of a biomarker of BCC. These results will provide critical preliminary data for a randomized controlled clinical trial using vitamin D3 for prevention of BCC tumors in Basal Cell Nevus Syndrome patients, which will be developed during the K award and submitted as a R34 grant application to the NIH at the end of Year 5. RELEVANCE (See instructions): Sunscreens do not prevent basal cell carcinomas of the skin, the most common cancer found in the US. Our goal is to determine whether vitamin D is an effective and safe agent to prevent basal cell carcinomas.