Dana Farber/Harvard Cancer Center SPORE in Lung Cancer

Dana Farber/哈佛大学癌症中心 SPORE 在肺癌中的应用

• 批准号: 10673920
• 负责人: David A Barbie
• 金额: $ 218.92万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10673920
• 关键词: Acceleration; Adaptive Immune System; Award; Basic Science; Biology; Boston; Cancer Center; Cancer Model; Cancer Patient; Cancer Vaccines; Cells; Cessation of life; Clinic; Clinical; Clinical Trials; Collaborations; Combined Modality Therapy; Community Hospitals; Couples; Dana-Farber Cancer Institute; Development; Disease; Drug Tolerance; Enrollment; Epidemiology; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Fostering; Foundations; Funding; General Hospitals; Generations; Geography; Goals; Grant; Hospitals; Immune Evasion; Immunotherapy; Individual; Infrastructure; Innate Immune System; Institution; Israel; Journals; Lung; Lung Adenocarcinoma; Malignant Neoplasms; Malignant neoplasm of lung; Massachusetts; Measures; Medical; Medical center; Mutation; Natural Immunity; Non-Small-Cell Lung Carcinoma; Oncogenes; Outcome; Patients; Pediatric Hospitals; Productivity; Protocols documentation; Public Health Schools; Publications; Research; Research Personnel; Resistance; SMARCA4 gene; Sampling; Signal Transduction; Site; Specialized Program of Research Excellence; Talents; Teaching Hospitals; Therapeutic; Therapeutic Studies; Time; Translating; Translations; Tumor Immunity; Tyrosine Kinase Inhibitor; United States National Institutes of Health; Vaccines; Woman; Work; adaptive immunity; biomarker driven; cancer clinical trial; cancer immunotherapy; career; cost; design; diversity and equity; effective therapy; immune checkpoint blockade; improved; inhibitor; innovation; inter-institutional; lung cancer screening; medical schools; member; mouse model; mutant; next generation; novel marker; overexpression; patient subsets; prevent; programmed cell death protein 1; programs; replication stress; senescence; synergism; targeted treatment; translational approach; translational goal; translational scientist; tumor DNA; tumor immunology

PROJECT SUMMARY This application is a resubmission of a Specialized Program of Research Excellence (SPORE) in Lung Cancer originating from the Lung Cancer Program of the Dana-Farber/Harvard Cancer Center (DF/HCC). The DF/HCC SPORE in Lung Cancer includes researchers from multiple Harvard-affiliated hospitals including the Dana- Farber Cancer Institute (DFCI), Massachusetts General Hospital (MGH), Beth Israel Deaconess Medical Center (BIDMC), Brigham and Women’s Hospital (BWH), and Boston Children’s Hospital (BCH), as well as Harvard Medical School (HMS) and Harvard T.H. Chan School of Public Health (HSPH). Previously, the DF/HCC Lung Cancer Program was funded by a Lung Cancer SPORE in 2002. This was followed by a successful renewal application in 2007 and a no-cost extension from 2013-2015. That period of time was accompanied by remarkable productivity by our investigators, including the initial description of epidermal growth factor receptor (EGFR) mutations by investigators at both MGH and DFCI, identification and development of 3rd generation EGFR tyrosine kinase inhibitors (TKIs) which are now in widespread clinical use, and rapid translation of effective ALK/ROS targeted therapies, among other accomplishments. However, despite the immense positive impact of targeted therapies, they have failed to cure advanced lung adenocarcinoma. Over the past 6 years since our prior SPORE ended, the DF/HCC lung program has evolved and grown ever more collaborative. We have maintained a developmental research program to support a new cadre of investigators, who have built strong additional arenas of expertise that add to our longstanding tradition of targeted therapy research in lung cancer, including innate and adaptive immunity, SCLC biology, circulating tumor DNA, and lung cancer screening. The DF/HCC Lung Cancer Program thus seeks SPORE funding to enable integrated teams that capitalize on the strengths of these new and established investigators to achieve our common goal of eliminating lung cancer deaths. The overarching goals of this SPORE are to: A) Design immunologic therapies that harness both the innate and adaptive immune systems to overcome ALK inhibitor resistance and enhance efficacy of PD-1 immune checkpoint blockade in non-small cell lung cancer (NSCLC) (Projects 1 and 2); B) Develop innovative approaches to EGFR and ALK-driven lung cancer with potential to improve long term survival via cancer vaccines or elimination of drug tolerant persister (DTP) cells or cancer vaccines (Projects 1 and 3); C) Co-opt vulnerabilities such as replication stress in SMARCA4 mutant NSCLC or a senescence program in EGFR TKI DTPs (Projects 2 and 3); D) Foster inter-institutional collaboration, including exchange of lung cancer models and patient samples (all Projects); and E) Continue to support and develop the next generation of lung cancer translational scientists from our talented group of fellows and early career investigators, with an emphasis on increasing diversity and equity.

项目概要 本申请是肺癌专业卓越研究计划 (SPORE) 的重新提交 源自丹娜—法伯癌症研究所/哈佛大学癌症中心 (DF/HCC) 的肺癌项目。 DF/HCC SPORE in Lung Cancer 包括来自多家哈佛附属医院的研究人员，其中包括丹纳- 法伯癌症研究所 (DFCI)、麻省总医院 (MGH)、贝斯以色列女执事医疗中心 (BIDMC)、布莱根妇女医院 (BWH)、波士顿儿童医院 (BCH) 以及哈佛大学 医学院 (HMS) 和哈佛大学 T.H.陈公共卫生学院 (HSPH)。此前，DF/HCC 肺 癌症计划于 2002 年由肺癌 SPORE 资助。随后成功更新 2007 年申请，2013-2015 年免费延期。那段时光伴随着 我们的研究人员的卓越生产力，包括表皮生长因子受体的初步描述 MGH 和 DFCI 研究人员进行的 (EGFR) 突变、第三代的鉴定和开发 EGFR酪氨酸激酶抑制剂（TKI）现已广泛应用于临床，并能快速转化为有效药物 ALK/ROS 靶向治疗等成就。然而，尽管产生了巨大的积极影响 靶向治疗未能治愈晚期肺腺癌。自我们成立以来的过去 6 年里 在 SPORE 结束之前，DF/HCC 肺部项目已经发展并变得更加协作。我们有 维持一项发展研究计划，以支持新的研究人员队伍，他们已经建立了强大的 其他专业领域增加了我们肺癌靶向治疗研究的长期传统， 包括先天性和适应性免疫、SCLC 生物学、循环肿瘤 DNA 和肺癌筛查。这 因此，DF/HCC 肺癌项目寻求 SPORE 资金，以使综合团队能够利用 这些新的和成熟的研究人员的优势，以实现我们消除肺癌的共同目标 死亡人数。该 SPORE 的总体目标是： A) 设计同时利用 先天性和适应性免疫系统可克服 ALK 抑制剂耐药性并增强 PD-1 的功效 非小细胞肺癌 (NSCLC) 中的免疫检查点阻断（项目 1 和 2）； B) 发展创新 治疗 EGFR 和 ALK 驱动的肺癌的方法有可能通过癌症疫苗改善长期生存 或消除耐药持久性 (DTP) 细胞或癌症疫苗（项目 1 和 3）； C) 增选 诸如 SMARCA4 突变 NSCLC 中的复制应激或 EGFR TKI 中的衰老程序等脆弱性 DTP（项目 2 和 3）； D) 促进机构间合作，包括交换肺癌模型 和患者样本（所有项目）； E) 继续支持和开发下一代肺癌 来自我们才华横溢的研究员和早期职业研究人员团队的转化科学家，重点是 增加多样性和公平性。