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

针对头颈部癌症患者的一项专门的卓越研究计划被提出，名为“头颈部生物学、治疗和预防的分子基础”，它将显著改善治疗结果，并降低与这种毁灭性的恶性肿瘤相关的发病率和死亡率。这些目标将通过改善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，对治疗的分子基础的了解的增加将允许更精确的个体化患者选择，这将导致更少的病态治疗和改善的生活质量，此外，还有可能更好地控制转移和更早发现或预防第二原发恶性肿瘤。 我们建议继续这一综合翻译研究计划，该计划由四个主要项目组成，分别探索1。对可能通过放疗或化疗治愈的患者进行更具体的治疗选择；新的小分子细胞凋亡调节抑制剂，以提高化疗/放射敏感性；通过制定完善的预防战略提高存活率；以及关键小分子和化学放射测序在优化治疗结果方面的作用。这些主要的翻译项目与正在进行的非常成功的职业发展和发展研究项目相辅相成。所有的孢子研究都得到了三个核心资源的支持，并在我们最初的资助期间取得了成功(管理和转译试验支持、生物统计学以及组织和组织病理学)。重点是通过利用已建立的运营委员会、高级咨询委员会和外部审查委员会，继续对所有计划和核心资源进行持续的科学审查，该委员会由癌症研究领域的专业基础和临床科学家组成。在我们最初的资助期内，强有力的机构承诺在此次续签申请中显著增加，以支持设备需求、我们的开发研究计划，并提供更大的灵活性，以进一步调查由于这些孢子项目和合作而取得的新发现。这个头颈部孢子是密歇根大学综合癌症中心的一个完全整合的组成部分。我们结合了癌症中心核心设施以及临床和实验室资源的广泛使用，并在很大程度上依靠经验丰富的癌症中心领导。由经验丰富的临床/基础合作者组成的一流团队，加上高度的机构承诺和优先事项，以及广泛的患者资源，提供了一个出色的研究环境，将确保在实现总体孢子目标方面继续取得成功。

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.