10 Lung Cancer

项目总结/摘要 肺癌计划（LCP）包括70名成员（34名主要成员，35名助理成员，1名助理成员）， 部门该计划由生物标志物驱动的临床试验专家John Heymach博士领导， 治疗靶向谁监督该计划;博士杰克罗斯，外科医生，科学家和共同PI的大学 和劳伦拜尔斯博士，谁领导该计划的临床研究工作和指导 学员研究员和初级教员LCP的主要科学目标是开发更有效的， 肺癌的治疗方法为了实现这一目标，该方案有三个具体目标 主要关注3个主题：1）肺癌信号传导和治疗靶点; 2）靶向免疫系统， 微环境;和3）局部和晚期肺癌的多模式治疗。年直接 同行评审的资金总额为570万美元，包括NCI肺癌SPORE，Stand Up 2癌症梦之队 奖和3个CPRIT多研究者研究奖。在总资金中，340万美元（60%）来自NCI赠款。 自上一次竞争性更新以来，年度同行评审的直接成本资金总额增加了93%。以来 截至上次提交，该计划已发表999篇论文：550（55%）计划内合作，355 (36 607项（61%）外部合作。44%的 出版物出现在IF >5的期刊上，15%出现在IF >10的期刊上，包括Science， N Engl J Med，Proc Natl Acad Sci USA，Cancer Discov，and Lancet Oncol.在最后一个项目期间， 成员在护理标准改变研究中发挥领导作用，包括AURA 3研究（建立 奥希替尼治疗EGFR T790 M突变型NSCLC）和一项证明局部巩固治疗获益的研究 寡转移性NSCLC患者的治疗。我们先前的发现确定了小细胞肺中的新靶点 癌症（SCLC）的治疗已经在随后的临床研究中得到验证。成员还确定了KRAS的3个子集- 突变型NSCLC基于共同发生的基因组改变，表现出不同的生物学、免疫- 系统参与和治疗弱点。最后，他们确定了上皮细胞到间充质细胞的作用， 通过miR 200/ZEB 1/PD-L1轴调节肿瘤免疫抑制的过渡，在肿瘤免疫抑制中发挥核心作用。 促进NSCLC转移。在未来几年，成员们将在这些发现的基础上， 靶向肺癌亚群的方法，重点关注SCLC和KRAS突变型NSCLC;研究 增强抗肿瘤免疫力和免疫治疗抗性机制的策略;并开发 整合免疫疗法和靶向药物的多学科范式，作为改善免疫治疗的方法。 肺癌患者的生存率。

PROJECT SUMMARY/ABSTRACT The Lung Cancer Program (LCP) includes 70 members (34 primary, 35 associate, 1 adjunct) from 19 departments. The program is led by Dr. John Heymach, an expert in biomarker-driven clinical trials and therapeutic targeting who oversees the program; Dr. Jack Roth, a surgeon-scientist and co-PI of the University of Texas Lung SPORE; and Dr. Lauren Byers, who leads the program's clinical research efforts and mentoring of trainees, fellows, and junior faculty. The major scientific goal of the LCP is to develop more effective and personalized approaches for the treatment of lung cancer. To achieve this goal, the program has 3 specific aims that focus on 3 themes: 1) lung cancer signaling and therapeutic targets; 2) targeting the immune system and microenvironment; and 3) the multimodal treatment of localized and advanced lung cancer. The annual direct peer-reviewed funding totals $5.7M, including an NCI Lung Cancer SPORE, a Stand Up 2 Cancer Dream Team Award, and 3 CPRIT Multi-Investigator Research Awards. Of the total funding, $3.4M (60%) is from NCI grants. Since the last competitive renewal, total annual peer-reviewed direct-cost funding has increased by 93%. Since the last submission, the program has published 999 papers: 550 (55%) intra-programmatic collaborations, 355 (36%) inter-programmatic collaborations, and 607 (61%) external collaborations. Forty-four percent of the publications appeared in journals with an IF >5, and 15% appeared in journals with an IF >10, including Science, N Engl J Med, Proc Natl Acad Sci USA, Cancer Discov, and Lancet Oncol. During the last grant period, program members had leadership roles in standard-of-care–changing studies, including the AURA3 study (establishing osimertinib for EGFR T790M–mutant NSCLC) and a study demonstrating the benefit of local consolidative therapy for patients with oligometastatic NSCLC. Our previous findings identifying novel targets in small cell lung cancer (SCLC) have been validated in subsequent clinical studies. Members also identified 3 subsets of KRAS- mutant NSCLC based on co-occurring genomic alterations that exhibit distinct biology, patterns of immune- system engagement, and therapeutic vulnerabilities. Finally, they identified a role for epithelial-to-mesenchymal transition in regulating tumor immunosuppression via an miR200/ZEB1/PD-L1 axis, playing a central role in promoting NSCLC metastasis. In upcoming years, members will build on these findings to identify new approaches to target subsets of lung cancer, with a focus on SCLC and KRAS-mutant NSCLC; investigate strategies for enhancing antitumor immunity and mechanisms of immunotherapy resistance; and develop multidisciplinary paradigms integrating immunotherapy and targeted agents as an approach to improve the survival of lung cancer patients.