INNOVATIVE TUMOR TARGETED THERAPIES FOR LUNG CANCER

本申请的目的是开发针对肺癌和支气管癌前病变的创新肿瘤靶向疗法。一般的假设是，结合联合收割机解剖和分子靶向的治疗策略应该构成这些病症的改进的治疗方式。 将采用三种主要的治疗策略：1）支气管癌前病变的吸入治疗，2）抑制在肺癌生长失调中起主要作用的途径，3）解剖靶向。在这三大战略范围内提出了三个原型项目：1）雾化脂质体/p53制剂在携带p53突变的肺癌和支气管癌前病变患者中的临床前和初始临床评价，2）化学疗法和抗EGFR单克隆抗体C225在IIIA期NSCLC中的协同作用的临床研究，3）胸腔内治疗在治疗IIB期NSCLC伴恶性胸腔积液患者中的应用。 所有这三个项目都包括临床试验的性能，这些试验包括测量可能与观察到的抗肿瘤作用相关的药理学或分子参数。 所提出的工作是申请人在过去十年中在药物递送和肺癌治疗研究领域的转化研究工作的逻辑延续。 具体项目将由申请人指导的年轻临床研究人员进行。根据这项建议，导师候选人将包括在纽约大学医学肿瘤学奖学金注册的研究员和血液科，肺科和外科的初级工作人员。已经确定了四名候选人。 预计在五年期间将指导总共十名年轻的临床研究人员。

The objective of this application is to develop innovative tumor- targeted therapies for lung cancer and bronchial premalignancy. The general hypothesis is that therapeutic strategies that combine anatomical and molecular targeting should constitute improved therapeutic modalities for these conditions. Three major therapeutic strategies will be pursued: 1) inhaled therapeutics for bronchial premalignancy, 2) inhibition of pathways that play a major role in lung cancer dysregulated growth, and 3) anatomical targeting. Three prototype projects within these three major strategies are proposed: 1) preclinical and initial clinical evaluation of an aerosolized liposome/p53 formulation in patients with lung cancer and bronchial premalignancy carrying p53 mutations, 2) clinical studies of synergism between chemotherapy and the anti-EGFR monoclonal antibody C225 in stage IIIA NSCLC, and 3) integration of intrapleural therapy in the treatment of patients with stage IIB NSCLC with malignant pleural effusion. All three projects include the performance of clinical trials that incorporate the measurement of pharmacological or molecular parameters potentially correlated with the observed antitumor effect. The work proposed is a logical continuation of the applicant's translational research efforts in the areas of drug delivery and lung cancer therapy research during the last decade. The specific projects will be conducted by young clinical investigators mentored by the applicant. Candidates for mentorship under this proposal will include fellows enrolled in the Medical Oncology fellowship at NYU and junior staff members of the Divisions of Hematology, Pulmonary Medicine, and Surgery. Four such candidates have already been identified. It is anticipated that a total of ten young clinical investigators will be mentored during a five-year period.