The Molecular Basis of Head and Neck Cancer Biology, Treatment and Prevention

一项针对头颈部癌症患者的卓越研究专门计划，题为“头颈部生物学、治疗和预防的分子基础”，该计划将显著改善治疗效果，降低与这种毁灭性恶性肿瘤相关的发病率和死亡率。这些目标将通过提高对分子生物学的理解和应用来实现，以检测，预防，治疗选择和开发头颈部癌症患者的新疗法。我们正在进行的假设是，增加对治疗的分子基础的理解将允许更精确的个体化患者选择，这将导致较少的病态治疗和改善生活质量，除了更好地控制转移和早期检测或预防第二原发恶性肿瘤的可能性。 我们建议继续这个综合转化研究计划，包括四个主要项目，探索1。为可能通过放射或化学疗法治愈的患者提供更具体的治疗选择; 2.）增加化疗/放射敏感性的新的小分子抗凋亡调节剂; 3.）通过制定健全的预防战略，提高生存率; 4.）关键小分子的作用和放化疗顺序优化治疗结果。这些主要的翻译项目是由正在进行的非常成功的职业发展和发展研究计划的补充。所有SPORE研究都得到了三个核心资源的支持，并在我们的初始资助期间取得了成功（管理和转化试验支持，生物统计学以及组织和组织学）。重点是通过利用由癌症研究领域的专家基础和临床科学家组成的已设立的业务委员会、高级咨询理事会和外部审查委员会，对所有方案和核心资源进行持续不断的科学审查。在我们的初始资助期内，强有力的机构承诺在这次更新申请中显着增加，以支持设备需求，我们的发展研究计划，并提供更大的灵活性，以进一步研究这些SPORE项目和合作所带来的新发现。这个头部和颈部孢子是密歇根大学综合癌症中心的一个完全集成的组成部分。我们广泛使用癌症中心的核心设施和临床及实验室资源，并大量利用经验丰富的癌症中心领导层。由经验丰富的临床/基础合作者组成的优秀团队，加上高度的机构承诺和优先权，以及广泛的患者资源，提供了一个出色的研究环境，将确保在实现总体SPORE目标方面持续取得成功。

A Specialized Program of Research Excellence for patients with cancer of the head and neck entitled "The Molecular Basis of Head and Neck Biology, Treatment and Prevention" is proposed that will significantly improve treatment results and reduce morbidity and mortality associated with this devastating malignancy. These goals will be achieved through improved understanding and application of molecular biology to the detection, prevention, treatment selection and development of new therapies for patients with head and neck cancers. Our ongoing hypothesis is that increased understanding of the molecular basis for treatment will allow more precise individualized patient selection that will result in less morbid therapy and improved quality of life, in addition to the possibility of better control of metastases and earlier detection or prevention of second primary malignancies. We propose continuation of this integrated translational research program consisting of four major projects that explore 1.) more specific treatment selection for patients likely to be cured with radiation or chemotherapy; 2.) new small molecule inhibitors of apoptosis-regulation to increase chemo/radiosensitivity; 3.) improved survival through development of sound prevention strategies; and 4.) the role of critical small molecules and chemoradiation sequencing for optimizing treatment results. These major translational projects are complemented by ongoing highly successful Career Development and Developmental Research Programs. All SPORE studies are supported by three Core Resources with demonstrated success in our initial funding period (Administration and Translational Trials Support, Biostatistics, and Tissue and Histopathology). Emphasis is placed on continued ongoing scientific review of all programs and core resources through utilization of an established Operations Committee, Senior Advisory Council and External Review Committee comprised of expert basic and clinician scientists in the field of cancer research. Strong institutional commitment in our initial funding period has been increased significantly in this renewal application to support equipment needs, our Developmental Research Program and provide increased flexibility to pursue further investigations of novel discoveries that are made as a result of these SPORE projects and collaborations. This Head and Neck SPORE is a fully integrated component of the University of Michigan Comprehensive Cancer Center. We have incorporated extensive use of Cancer Center core facilities and clinical and laboratory resources, and we draw heavily on experienced Cancer Center leadership. Superb teams of experienced clinical / basic collaborators combined with high institutional commitment and priority, and extensive patient resources provide an outstanding research environment that will ensure continued success in achieving overall SPORE goals.