A Novel Modular Polymer Platform for the Treatment of Oral SCCA

用于治疗口腔 SCCA 的新型模块化聚合物平台

• 批准号: 8292962
• 负责人: MAIE A ST JOHN
• 金额: $ 12.66万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8292962
• 关键词: Address; Aftercare; Antibodies; Apoptosis; Beds; Biocompatible; CCL21 gene; CXCR4 gene; Cancer cell line; Cell Proliferation; Cell surface; Cessation of life; Characteristics; Cisplatin; Clinical; Clinical Research; Clinical Trials; Data; Development; Disease; Doctor of Medicine; Doctor of Philosophy; Enrollment; Environment; Evaluation; Excision; Faculty; Failure; Flow Cytometry; Funding; Future; Goals; Human; Immune system; Immunomodulators; In Vitro; Individual; Interleukin-7; Investigation; Ionizing radiation; Kinetics; Label; Laboratories; Left; Malignant Neoplasms; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Modeling; Molecular Target; Nature; Neoplasm Metastasis; Operative Surgical Procedures; Oral; Oropharyngeal Squamous Cell Carcinoma; Outcome; Patients; Pharmaceutical Preparations; Pilot Projects; Polymers; Positioning Attribute; Postoperative Period; Public Health; Quality of life; Radiation; Radiation Oncologist; Radiation therapy; Recurrence; Research; Research Personnel; Research Project Grants; Risk; SCID Beige Mouse; Scientist; Staining method; Stains; Stem cells; Structure; Surface; Surgeon; Survival Rate; Testing; Therapeutic; Training Programs; Translational Research; Tumor Burden; Tumor Debulking; Unresectable; Validation; attributable mortality; base; cancer diagnosis; cancer surgery; cancer therapy; career; caspase-3; cell killing; chemotherapeutic agent; clinically relevant; cytotoxic; design; didactic education; embryonic stem cell; immune activation; improved; in vivo; killings; malignant mouth neoplasm; malignant oropharynx neoplasm; member; mortality; neoplastic cell; novel; oncology; patient oriented research; professor; prospective; prototype; public health relevance; radiation effect; treatment strategy; tumor; tumor progression

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.

描述（由申请人提供）：Maie St. John，医学博士，博士是加州大学洛杉矶分校的外科助理教授，临床重点是口腔和口咽癌。她的职业目标是：1）研究-在理解口腔癌肿瘤进展和转移机制的转化应用中开发科学组合：将她基于实验室的研究结果纳入OSCC新疗法的开发;并成熟为能够成功竞争资金的独立科学家。2)临床-成为口腔和口咽癌手术的学术领导者，以患者为导向的研究而闻名。为了实现这些目标，她将接受Steven M.的指导。Dubinett，医学博士和Cun-Yu Wang，DDS，PhD，以及由资深教师组成的指导委员会。她将在一个高度保护，刺激的研究环境，致力于口腔癌的转化研究。她就读于加州大学洛杉矶分校K30研究生培训计划在翻译研究，以获得临床研究学位，在翻译和患者为导向的研究个性化的教学课程。她的研究项目需要开发一种新型的生物相容性模块化聚合物平台，这将改善晚期或复发性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提出了相当大的挑战。这种情况下的手术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，尽可能多地缩小大肿瘤并留下不可切除的部分。不幸的是，在这些情况下，局部失效至少为40%或更高。降低死亡率、提高这些患者的生活质量和生存率的能力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物，具有以下特点：生物相容性;可缓慢降解;可以作为一个平台，提供免疫调节剂和化疗剂，以便最有效地杀死聚合物应用附近的肿瘤细胞。该聚合物包裹物设计用于在切除或减积肿瘤后术中应用于手术床，从而允许增强术后放射治疗，并且还用作递送免疫调节剂的平台。除了其临床相关特征外，这种聚合物平台的模块化性质为未来的研究提供了一种优雅的方法，可以识别特定的分子靶标。最终的验证将是在一个前瞻性试验的背景下，在患者不可切除的晚期或复发性口腔鳞癌。 公共卫生关系：口腔鳞状细胞癌是世界上第六大常见癌症，口腔鳞状细胞癌患者的死亡风险相当大，每年有超过30万人死于该疾病。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，可以满足这种疾病对新疗法的需求。