A Novel Modular Polymer Platform for the Treatment of Oral SCCA

描述(由申请人提供)：Maie St.John，医学博士，加州大学洛杉矶分校外科助理教授，主要从事口腔和口咽癌的临床研究。她的职业目标是：1)研究-开发了解口腔癌肿瘤进展和转移机制的翻译应用的科学组合：将她基于实验室的研究结果纳入口腔鳞癌新疗法的开发；并成长为一名能够成功竞争资金的独立科学家。2)临床-成为口腔和口咽癌外科领域的学术领导者，以患者为中心的研究而闻名。为了实现这些目标，她将接受史蒂文·M·杜比奈特医学博士和王存玉博士的指导，以及由资深教员组成的指导委员会的指导。她将在一个高度保护、激励的研究环境中致力于口腔癌的翻译研究。她参加了加州大学洛杉矶分校K30翻译研究研究生培训计划，获得了临床研究学位，并开设了翻译和患者导向研究的个性化教学课程。她的研究项目要求开发一种新型的生物兼容模块化聚合物平台，该平台将改善晚期或复发的口腔和口咽鳞状细胞癌(OSCC)患者的预后。这些患者的管理对外科医生和放射肿瘤学家构成了相当大的挑战。在这种情况下，外科手术的要求是更广泛的切除，或者在某些情况下，当肿瘤固定在下面的重要结构上时，尽可能多地清除大肿瘤，留下不能切除的部分。不幸的是，在这些情况下，局部故障至少有40%或更多。能够降低死亡率，提高这些患者的生活质量和生存质量一直是一个长期的目标。圣约翰博士开发了一种聚合物包裹，具有以下特点：生物相容性；可缓慢降解；并可作为输送免疫调节剂和化疗药物的平台，以便最有效地杀死聚合物应用附近的肿瘤细胞。这种聚合物包被设计为在切除或去除肿瘤后，在手术中应用于手术床上，从而允许加强术后放射治疗，并作为输送免疫调节剂的平台。除了与临床相关的特点外，这种聚合物平台的模块化特性为未来的研究提供了一种优雅的方法，允许识别特定的分子靶标。最终的验证将在不能切除的晚期或复发口腔鳞癌患者的前瞻性试验的背景下进行。 公共卫生相关性：口腔鳞状细胞癌是世界上第六大最常见的癌症，口腔鳞状细胞癌患者有相当大的死亡风险，每年有30多万人死于这种疾病。在过去的30年里，晚期口腔鳞癌患者的3-5年生存率一直很低(20%-30%)。这种模块化聚合物平台是一种新的治疗策略，满足了这种疾病对新疗法的需求。

DESCRIPTION (provided by applicant): Maie St. John, MD, PhD is an Assistant Professor of Surgery at UCLA with a clinical focus in oral and oropharyngeal cancer. Her career goals are: 1) Research - To develop a scientific portfolio in translational applications of the understanding of mechanisms of tumor progression and metastasis in oral cancer: incorporating the results of her laboratory-based research into the development of novel therapies for OSCC; and to mature into an independent scientist who can successfully compete for funding. 2) Clinical - To become an academic leader in oral & oropharyngeal cancer surgery known for patient oriented research. In order to achieve these goals, she will receive mentorship from Steven M. Dubinett, M.D. and Cun-Yu Wang, DDS, PhD, and the mentoring committee comprised of senior faculty members. She will be in a highly protected, stimulating research environment devoted to translational research in oral cancer. She is enrolled in the UCLA K30 Graduate Training Program in Translational Investigation to receive a degree in Clinical Research with an individualized didactic curriculum in translational and patient oriented research. Her research project entails the development of a novel biocompatible modular polymer platform which will improve the outcome for patients with advanced or recurrent Oral and Oropharyngeal Squamous Cell Carcinomas (OSCC). The management of these patients poses a considerable challenge to the surgeon and the radiation oncologist. The surgical demand in such a setting is for wider resection or, in some instances when the tumor is fixed to the underlying vital structures, to debulk as much of a large tumor as possible and leave behind the unresectable portions. Unfortunately, local failure in these cases is at least 40% or greater. The ability to decrease mortality, and improve quality of life and survival for these patients has been a longstanding goal. Dr. St. John has developed a polymer wrap that has the following characteristics: is biocompatible; is slowly degradable; and can serve as a platform to deliver immunomodulators and chemotherapeutic agents so as to most effectively kill tumor cells in the proximity of the polymer application. This polymer wrap is designed to be applied intraoperatively to the surgical bed after removing or debulking the tumor, thus allowing for enhanced post-operative radiation treatment, and also functioning as a platform for the delivery of immunomodulators. Besides its clinically relevant features, the modular nature of this polymer platform provides an elegant approach to future investigations, allowing the identification of specific molecular targets. The ultimate validation will be in the context of a prospective trial in patients with unresectable advanced or recurrent OSCC. PUBLIC HEALTH RELEVANCE: OSCC is the sixth most common cancer in the world, and patients with OSCC are at considerable risk of mortality, with more than 300,000 deaths attributable to the disease annually. During the past 30 years, the 3- to 5-year survival rate of patients with advanced OSCC has remained poor (20-30%). This modular polymer platform is a novel treatment strategy that addresses the need for new therapies in this disease.