Cancer Targets and Drug Discovery

癌症靶点和药物发现

• 批准号: 10443758
• 负责人: Nicholas David Cosford
• 金额: $ 24.66万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-03 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10443758
• 关键词: Malignant Neoplasms; drug discovery; Malignant Neoplasms; drug discovery

T32 Proposal “Cancer Targets and New Drug Discovery” ABSTRACT The goal of the T32 training program “Cancer Targets and New Drug Discovery” is to establish an innovative multi-thematic graduate student and postdoctoral training program (“the Program”) to train the next generation of leaders in cancer target discovery and validation, cancer drug discovery, and biomarker development. This goal will be attained by a 2 year training program for 1 graduate student and 3 postdoctoral trainees, who will be trained in the skills needed to execute a successful cancer drug discovery program using novel paradigms and state-of-the-art technologies. The program uniquely includes a 2-month biotech company internship and training in scientific entrepreneurship specifically focused on new cancer target and drug discovery, as well as research entrepreneurship. The Specific Aims of the Program are: 1) To discover and validate novel cancer drug targets. Training will focus on critically validating new targets in the context of signaling networks, mechanisms of genetic and epi-genetic regulation, and also on exploring non-traditional targets, for example, targeting components of tumor stroma, which is important for supporting cancer cell growth and providing a barrier to attack by immune cells. The genetic stability of the stroma may also render the putative targets less susceptible to developing resistance; 2) To discover small molecule probes to interrogate novel cancer targets. SBP has the technically most advanced and largest chemical library screening program of any academic organization. Our strong expertise in structurally-based rational drug design using NMR and X-ray crystallography will provide training opportunities in probe discovery using both approaches; 3) To conduct mechanistic studies of cancer signaling pathways using probe inhibitors. We will provide training in the use of small molecule probes in cells and preclinical animal models to provide insights into the practical application of drugs to treat cancer, signaling interactions, mechanisms of resistance and potential biomarkers; and 4) To provide entrepreneurial training. Given that fewer than 15% of trainees can expect to have a faculty appointment in academia, we will provide the trainees experience in biopharma research as a possible alternate career. We are located in the second largest hub of biotech companies in the United States, and working with a corporate biotech incubator partner, will provide a unique entrepreneurial T32 training experience with a 2-month cancer biotech internship.

T32提案“癌症靶标和新药物发现” 抽象的 T32培训计划“癌症目标和新药发现”的目标是建立创新的 多主题研究生和博士后培训计划（“计划”）培训下一代 癌症目标发现和验证，癌症药物发现和生物标志物发育领域的领导者。这 目标将由一项为1名研究生和3名博士后学员的2年培训计划附加到目标，他们将 接受使用新型范式执行成功的癌症药物发现计划所需的技能培训 和最先进的技术。该计划独特地包括一个2个月的生物技术公司实习， 专门针对新的癌症目标和药物发现的科学企业家培训以及 研究企业家精神。该程序的具体目的是：1）发现和验证新型癌症 药物靶标。培训将集中于在信号网络的背景下批判性验证新目标， 遗传和表观遗传调节的机制，以及探索非传统目标的机制 靶向肿瘤基质的成分，这对于支持癌细胞生长并提供 免疫细胞攻击的障碍。基质的遗传稳定性也可能使推定的靶标更少 容易受到抗药性的影响； 2）发现小分子问题以询问新的癌症靶标。 SBP具有任何学术上最先进和最大的化学图书馆筛选计划 组织。我们在基于结构的理性药物设计方面使用NMR和X射线的强大专业知识 晶体学将使用这两种方法为探针发现提供培训机会。 3）进行 使用探针抑制剂对癌症信号通路的机理研究。我们将提供使用的培训 细胞和临床前动物模型中的小分子问题，以提供有关实际应用的实际应用 治疗癌症，信号相互作用，抗药性机制和潜在生物标志物的药物；和4）到 提供创业培训。鉴于不到15％的学员可以期望拥有一名教师 在学术界任命，我们将提供生物制药研究的实习生体验 替代职业。我们位于美国第二大生物技术公司中心， 与公司生物技术孵化器合作伙伴合作将提供独特的企业家T32培训 具有2个月的癌症生物技术实习经验。