Cancer Targets and Drug Discovery

T32提案“癌症靶点和新药发现” 摘要 T32培训计划“癌症靶点和新药发现”的目标是建立一个创新的 多主题研究生和博士后培养计划（“计划”），以培养下一代 癌症靶点发现和验证、癌症药物发现和生物标志物开发领域的领导者。这 目标将通过为期2年的培训计划实现1名研究生和3名博士后实习生，他们将 接受使用新范式执行成功的癌症药物发现计划所需技能的培训 和最先进的技术。该计划独特地包括为期2个月的生物技术公司实习， 科学创业培训专门侧重于新的癌症靶点和药物发现，以及 研究创业。该计划的具体目标是：1）发现和验证新的癌症 药物靶点培训将侧重于在信令网络的背景下批判性地验证新目标， 遗传和表观遗传调节机制，以及探索非传统靶点，例如， 靶向肿瘤间质的成分，这对于支持癌细胞生长和提供 免疫细胞攻击的屏障。间质的遗传稳定性也可能使假定的靶点较少 易产生耐药性; 2）发现小分子探针来询问新的癌症靶点。 SBP拥有技术上最先进和最大的化学图书馆筛选计划的任何学术 organization.我们在使用NMR和X射线进行基于结构的合理药物设计方面的强大专业知识 晶体学将提供使用这两种方法发现探针的培训机会; 3）进行 使用探针抑制剂的癌症信号通路的机制研究。我们将提供使用 小分子探针在细胞和临床前动物模型中的应用， 治疗癌症的药物、信号相互作用、耐药性机制和潜在的生物标志物;以及4） 提供创业培训。考虑到只有不到15%的受训者可以指望有一个教师， 在学术界的任命，我们将提供学员在生物制药研究的经验，作为可能的 替代职业我们位于美国第二大生物技术公司中心， 与企业生物技术孵化器合作伙伴合作，将提供独特的创业T32培训 有2个月的癌症生物技术实习经验。

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.