Cancer Biology

项目概要/摘要-癌症生物学项目 癌症生物学计划（CBP）的首要目标是探索和了解癌症的细胞生物学。 癌为了实现这一目标，我们领导综合和跨学科的努力，以确定相关的途径 确定驱动突变和遗传异常作为治疗靶向的新线索，并探索 并利用抗癌机制作为转化为临床试验的途径。该项目由Martine F. 他是国际公认的细胞周期G1期调控专家， 与儿科癌症相关的细胞增殖，以及道格拉斯·R.绿色，博士，世界著名的科学家研究 决定细胞死亡和存活的机制，包括凋亡、坏死性凋亡、自噬和 癌症和免疫系统的代谢。他们共同努力将发现研究转化为临床 通过促进科学交流，我们的成员和其他癌症成员之间的合作， 中心计划，并积极参与我们的会员会议。CBP成员组织成 制定了四个方案工作组，以解决在了解儿科癌症方面未满足的需求 生物学：癌细胞信号网络和治疗，细胞死亡，细胞应激修复和 代谢，肿瘤微环境和免疫学，基因组结构和功能。CBP已 29名成员，包括来自12个部门的21名正式成员和8名准成员（初级指导）。 在目前的资助期间，CBP的研究已经产生了570个主要研究出版物，其中 23.9%是跨方案的，表明CBP成员在支持以疾病为重点的 通过基础发现进行的研究中，12.8%是计划内的，76.5%是机构间的（与其他机构一起）。 NCI-designated Cancer Centers）。38%的研究论文发表在影响因子>10的期刊上。这 工作包括所有儿科癌症的基因组景观，通过发展儿科癌症 基因组计划揭示了表观遗传调节因子在癌症中的关键作用， 细胞死亡和细胞存活的机制，并阐明影响细胞存活的先天性和适应性免疫功能。 我们对抗癌免疫的理解。CBP成员总共拥有600万美元的同行评审资金。CBP 成员们已经取得了一些基础科学发现已转化为临床，大大 通过与其他SJCCC计划的互动促进。这包括FDA目前批准的CDK 4/6抑制剂 在治疗乳腺癌的临床试验中， 与NBTP成员合作治疗高危髓母细胞瘤。因为SJCCC专注于 研究人员专门针对儿科癌症进行研究和开发各种儿科癌症的试验， 利用各种治疗方法。因此，我们的工作组是广泛的， 最大限度地利用合作翻译的机会，并将该计划定位于解决机会 和优先事项。

PROJECT SUMMARY/ABSTRACT–Cancer Biology Program The overarching goal of the Cancer Biology Program (CBP) is to explore and understand the cell biology of cancer. In working toward this goal, we lead integrated and transdisciplinary efforts to define pathways related to cancer, identify driver mutations and genetic anomalies as new leads for therapeutic targeting, and explore and exploit anti-cancer mechanisms as routes to translation into clinical trials. The Program is led by Martine F. Roussel, PhD, an internationally recognized expert on the regulation of the G1 phase of the cell cycle and proliferation as it relates to pediatric cancers, and Douglas R. Green, PhD, a world-renowned scientist studying the mechanisms that dictate cell death and survival, including apoptosis, necroptosis, autophagy, and metabolism in cancer and the immune system. They work together to translate discovery research to the clinic by stimulating scientific exchanges, collaborations between our members and members of the other Cancer Center Programs, and the active participation of our membership in meetings. CBP members are organized into four programmatic working groups formulated to address unmet needs in the understanding of pediatric cancer biology: Cancer Cell Signaling Networks and Therapeutics, Cell Death, Cell Stress Repair and Metabolism, Tumor Microenvironment and Immunology, and Genome Structure and Function. CBP has 29 members, including 21 Full Members and 8 Associate Members (junior mentored) from 12 Departments. During the current funding period, research in CBP has resulted in 570 primary research publications, of which 23.9% were inter-programmatic, demonstrating the key role of CBP members in supporting disease-focused research through basic discovery, 12.8% were intra-programmatic, and 76.5% were inter-institutional (with other NCI-designated Cancer Centers). 38% of our research publications were in journals with impact factor >10. This work includes the genomic landscape of all pediatric cancers through the development of the Pediatric Cancer Genome Project that unraveled the critical role of epigenetic regulators in cancer, fundamental insights into mechanisms of cell death and cell survival, and elucidation of innate and adaptive immune functions impacting our understanding of anti-cancer immunity. CBP members have a total of $6M in peer-reviewed funding. CBP members have made a number of basic science discoveries have been translated into the clinic, greatly facilitated by interactions with other SJCCC Programs. This includes FDA-approval of CDK4/6 inhibitors currently in clinical trials for treatment of breast cancer and the repurposing of gemcitabine and pemetrexed for the treatment of high risk medulloblastoma in collaboration with members of the NBTP. Because SJCCC is focused solely on pediatric cancer, investigators study and develop trials for a diverse spectrum of pediatric cancers utilizing a full array of therapeutic approaches. Consequently, our working groups are broad by design to maximize opportunities for collaborative translation and to position the program well to address opportunities and priorities as they emerge.