MOLECULAR BREAST CANCER THERAPY AND CARCINOGENESIS

这项提议的主要目标是开发一个具有凝聚力的、 希望之城癌症研究中心的多学科乳腺癌项目 中心(COH)。从1985年到1992年(其最后一个历年 有明确数据可用)，乳腺癌人口从 占COH癌症患者总数的15%至25%；绝对 就新发乳腺癌而言，这意味着从242例增加到478例。 每年对患者进行评估。乳腺癌患者现在体现了 在我们机构治疗的最常见的一种诊断。这一增长 伴随着病人数量的显著增加， 与乳腺癌相关的临床和实验室研究在COH。因此， 建议发展基础设施以支持新的 癌症中心计划，将重点放在交互式、调查性基础、 乳腺癌的临床和癌症控制倡议。世界银行的目标是 正在开展的COH乳腺癌研究计划是：(1)完成 乳腺癌患者在以下领域的创新临床试验 基因治疗、放射免疫治疗、大剂量自体化疗 外周血祖细胞拯救、生化调节和药物 抗药性逆转；(2)新基因的临床前研究 递送系统和基因导向的乳腺癌治疗，新的单抗 抗癌胚抗原抗体及其他乳房抗体 肿瘤抗原与乳腺癌药物的分子药理学 针对持续开发新的治疗药物的抗药性 以及(3)研究导致这种疾病的分子事件 乳腺癌的发生与提高乳腺癌的诊断和控制水平 癌症。基于大量患者资源的可用性，经过验证的 从复杂的、创新的机构乳腺癌累加的记录 临床试验，以及丰富的生产基础和临床历史 分子药理学、分子免疫学、 直接应用于肿瘤生物学、病毒学和癌症控制 为了提高乳腺癌患者的治疗效果，我们 建议在希望之城统一乳腺癌研究。增长 COH乳腺癌研究计划的成熟将集中于 兴趣和促进发展的强烈互动的研究 有潜力为减排做出重要贡献的团队 乳腺癌的发病率和死亡率。

The principal goal of this proposal is to develop a cohesive, multidisciplinary breast cancer program at the City of Hope Cancer Research Center (COH). From 1985 to 1992 (the last calendar year for which definitive data are available), the breast cancer population increased from 15 to 25% of the entire cancer patient population at COH; in absolute terms, this represented an increase from 242 to 478 new breast cancer patients evaluated per year. Patients with breast cancer now embody the single most common diagnosis treated at our institution. This increase in patient volume has been accompanied by a remarkable increase in the extent of breast cancer-related clinical and laboratory research at the COH. Thus, it is appropriate to propose to develop the infrastructure to support a new Cancer Center program that will focus on interactive, investigative basic, clinical, and cancer control initiatives in breast cancer. The goals of the developing COH Breast Cancer Research Program are: (1) to complete innovative clinical trials in patients with breast cancer in the areas of gene therapy, radioimmunotherapy, high-dose chemotherapy with autologous peripheral blood progenitor cell rescue, biochemical modulation, and drug resistance reversal; (2) to perform pre-clinical studies of novel gene delivery systems and gene-directed breast cancer therapies, new monoclonal antibodies against the carcinoembryonic antigen as well as other breast cancer antigens, and the molecular pharmacology of breast cancer drug resistance aimed at the continuing development of new therapeutic agents for this disease; and (3) to investigate the molecular events leading to breast carcinogenesis and improve the diagnosis and control of breast cancer. Based on the availability of a large patient resource, a proven track record of accrual to complex, innovative institutional breast cancer clinical trials, and a strong history of productive basic and clinical research interactions in molecular pharmacology, molecular immunology, tumor biology, virology, and cancer control that have been applied directly to enhance the therapeutic outcome for patients with breast cancer, we propose to unify breast cancer research at the City of Hope. The growth and maturation of the COH Breast Cancer Research Program will focus the interests and facilitate the development of a strongly interactive research team with the potential to make an important contribution to the reduction of breast cancer incidence and mortality.