Chemoprevention of basal cell carcinoma with vitamin D

描述(申请人提供)：这是加州大学旧金山分校的皮肤科医生Jean Tang申请K23奖项。唐博士在预防基底细胞癌(BCC)方面以患者为导向的转化性研究确立了自己作为年轻研究员的地位。这项K23奖项将为唐博士提供必要的支持，以实现以下目标：(1)进行用于预防基底细胞癌的维生素D的小鼠临床前试验；(2)对具有维生素D基线测量的大量预期老年男性队列进行二次数据分析；(3)在人体上进行试点临床试验，以测试外用或口服维生素D3的可行性。为了实现这些目标，唐博士组建了一个指导团队，成员包括主要导师、奥克兰研究所儿童医院科学家埃尔文·爱泼斯坦博士(Dr.Ervin Epstein)和三位共同导师：旧金山协调中心主任史蒂文·卡明斯博士(Steven Cummings)，他是临床研究和大规模患者队列试验的专家；玛丽-玛格丽特·克伦(Mary-Margaret Chren)博士，皮肤病结果研究专家；查尔斯·麦卡洛(Charles McCullough)博士，他擅长纵向数据分析和生物统计学。目前，还没有有效的药物来预防基底细胞癌。防晒霜还没有被证明可以预防基底细胞癌；然而，最近的体外数据表明，维生素D3抑制了基底细胞癌中发现的异常信号通路。唐博士已经证明，在小鼠身上局部应用维生素D3可以防止50%的基底细胞癌。在这本K23中，她建议确定抑制小鼠基底细胞癌的维生素D3的最佳给药途径(目标1)，并确定高水平的血清维生素D是否降低老年男性的基底细胞癌风险(目标2)。唐博士还将进行一项试点临床试验，以测试外用和口服维生素D3对有多个基底细胞瘤的基底细胞痣综合征患者的可行性(目标3)。从小鼠临床前试验和人类试验中，我们将确定维生素的最佳给药方式 D3用于抑制基底细胞癌的生物标志物。这些结果将为使用维生素D3预防基底细胞痣综合征患者基底细胞癌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，并在第五年年底作为R34拨款申请提交给NIH。相关性(参见说明)：防晒霜不能预防皮肤基底细胞癌，这是美国发现的最常见的癌症。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.