Cancer Evolution and Combinatorial Cancer Therapies: Concepts and Challenges

癌症进化和组合癌症疗法：概念和挑战

• 批准号: 9911129
• 负责人: Thale Cross Jarvis
• 金额: $ 0.5万
• 依托单位: KEYSTONE SYMPOSIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-15 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9911129
• 关键词: Advanced Development; Alberta province; Area; Automobile Driving; Canada; Cells; Clinical; Clinical Trials; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Computer Models; Dependence; Development; Educational workshop; Emerging Technologies; Epigenetic Process; Evolution; Fostering; Genomics; Goals; Human; Immune checkpoint inhibitor; Immunooncology; Immunotherapeutic agent; Immunotherapy; Investigation; Knowledge; Lead; Learning; Malignant Neoplasms; Maps; Measures; Metastatic to; Methodology; Mutation; Outcome; Output; Patients; Physicians; Population Heterogeneity; Pre-Clinical Model; Process; Regimen; Research; Research Personnel; Resistance; Role; Sampling; Science; Scientist; Site; Technology; Testing; Therapeutic; Therapeutic Studies; Tumor stage; base; cancer genetics; cancer heterogeneity; cancer therapy; clinical application; clinical development; clinical practice; combinatorial; drug discovery; functional genomics; genetic selection; genome-wide; genomic data; improved; novel strategies; posters; pre-clinical; preclinical development; programs; screening; small hairpin RNA; symposium; targeted treatment; therapy resistant; translational scientist; tumor; tumor heterogeneity; tumor progression

ABSTRACT Support is requested for a Keystone Symposia conference entitled Cancer Evolution and Combinatorial Cancer Therapies: Concepts and Challenges, organized by Drs. William Sellers, Charles Swanton and Lillian Siu. The conference will be held in Banff, Alberta Canada from January 19-23, 2020. Progress in understanding the clonal and sub-clonal processes driving tumor evolution, tumor heterogeneity, the mechanisms of therapeutic resistance, and in defining new cancer dependencies have converged to help inform more rational approaches to achieving the development of transformative combination therapeutic regimens in cancer. Nonetheless, examples of highly effective rationally elucidated combinations remain rare and the pre-clinical and clinical development challenges to this goal are substantial. As an example, the emergent role of immunotherapeutics having curative potential has led to tremendous excitement, yet increased complexity. The broad swath of empiric based clinical trials attests to the continued and growing need for improved pre-clinical means by which transformative combinations can be identified. This conference will bring together evolutionary and computational biologists, experts in functional genomics, translational scientists, drug discovery researchers and physician leaders in clinical development. The conference program begins with how evolutionary processes drive the “natural” progression of cancer and how such processes lead to the measured heterogeneous populations of cells resident in all tumors. These two related forces, driven at least in part by ongoing mutational processes, then combine to give rise to therapeutic resistance, which enables researchers to robustly identify mechanisms relevant to humans in pre-clinical models. The deeper understanding of these forces can inform specific combination therapeutics, but combination hypotheses are now being discovered though genome-scale functional screening approaches (e.g. CRISPR, shRNA). Speakers have been invited to discuss the studies which are now taking place in both the targeted and immuno-oncology (I/O) therapeutic fields. These talks filter into sessions on understanding how I/O and targeted therapeutics are similar or distinct and to seek the lessons from the clinical trial outputs in the I/O field that will emerge over the next year. Finally, clinical development paradigms for more rapidly testing and developing combinations will be covered during the conference.

摘要 请求为题为癌症进化和组合的Keystone研讨会提供支助 癌症治疗：概念和挑战，由William Sellers博士、Charles Swanton博士和Lillian博士组织 萧伯纳。大会将于2020年1月19日至23日在加拿大艾伯塔省班夫举行。 克隆和亚克隆过程推动肿瘤进化、肿瘤异质性、 治疗耐药的机制，以及在定义新的癌症依赖性方面，已经收敛到帮助 提出更合理的方法来实现变革性联合治疗的发展 癌症中的养生法。尽管如此，高效合理阐明的组合的例子仍然很少见。 而实现这一目标的临床前和临床开发挑战是巨大的。作为一个例子， 具有治愈潜力的免疫疗法的紧急作用导致了巨大的兴奋，但 增加了复杂性。大量基于经验的临床试验证明了这种持续和不断增长的趋势。 需要改进的临床前手段，通过这些手段可以确定变革性的组合。 这次会议将汇集进化和计算生物学家，功能基因组学专家， 翻译科学家、药物发现研究人员和临床开发方面的医生领导。这个 会议计划以进化过程如何驱动癌症的“自然”进展以及如何 这样的过程导致了所有肿瘤中存在的测量到的异质细胞群体。这两个 相关的力量，至少部分是由正在进行的突变过程驱动的，然后结合起来产生治疗 耐药性，这使研究人员能够有力地识别与临床前人类相关的机制 模特们。对这些力量的深入了解可以为特定的联合疗法提供信息，但 通过基因组规模的功能筛选方法，现在正在发现组合假说 (例如CRISPR、shRNA)。演讲者已被邀请讨论目前正在两地进行的研究 靶向和免疫肿瘤(I/O)治疗领域。这些会谈渗透到关于理解的会议中 I/O和靶向疗法是如何相似或不同的，并从临床试验结果中寻找经验教训 明年将出现的I/O字段。最后，临床发展范式更快 会议期间将讨论测试和开发组合。