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.

项目摘要 该应用程序是肺癌研究卓越研究（Spore）专业计划的重新提交 起源于Dana-Farber/Harvard Cancer Center（DF/HCC）的肺癌计划。 DF/HCC 肺癌中的孢子包括来自哈佛大学相关医院的研究人员，包括达纳 - 马萨诸塞州综合医院（MGH）的Farber癌症研究所（DFCI），贝丝以色列执事医疗中心 （BIDMC），杨百翰和妇女医院（BWH）和波士顿儿童医院（BCH）以及哈佛 医学院（HMS）和哈佛T.H.陈公共卫生学院（HSPH）。以前，DF/HCC肺 癌症计划在2002年由肺癌孢子资助。随后是成功的续签 2007年的申请以及2013 - 2015年的无成本扩展。那个时期是由 我们的研究人员的显着生产率，包括表皮生长因子受体的最初描述 （EGFR）研究人员在MGH和DFCI中的突变，第三代的识别和开发 EGFR酪氨酸激酶抑制剂（TKI）现在处于宽度临床中，并快速翻译有效 ALK/ROS靶向疗法以及其他成就。但是，要影响 有针对性的疗法，他们无法治愈晚期肺腺癌。自从我们的过去6年中 先前的孢子结束了，DF/HCC肺结计划已经发展和成长越来越多。我们有 维护了一项发展研究计划，以支持新的研究人员，他们建立了强大的研究人员 其他专业知识领域增加了我们在肺癌中有针对性治疗研究的长期传统， 包括先天和适应性免疫学，SCLC生物学，循环肿瘤DNA和肺癌筛查。这 因此，DF/HCC肺癌计划寻求孢子资金，以使综合团队能够利用 这些新的和既定的研究人员的优势，以实现我们消除肺癌的共同目标 死亡人数。该孢子的总体目标是：a）设计免疫疗法，既利用 先天性和适应性免疫系统，以克服PD-1的ALK抑制剂耐药性和增强效率 非小细胞肺癌（NSCLC）中的免疫检查点阻滞（项目1和2）； b）发展创新 EGFR和ALK驱动的肺癌的方法有可能通过癌症疫苗改善长期存活率 或消除药物耐药持久性（DTP）细胞或癌症疫苗（项目1和3）； c）选择 SMARCA4突变体NSCLC中的复制应力等脆弱性或EGFR TKI中的感应程序 DTP（项目2和3）； d）培养机构间合作，包括肺癌模型的交换 和患者样本（所有项目）； e）继续支持和发展下一代肺癌 来自我们才华横溢的研究员和早期职业调查员的翻译科学家，重点是 增加多样性和公平性。