Targeting Transcription and Splicing in Cancer

总体来说 项目总结 该计划的总体目标是了解转录和剪接调控是如何改变的，并共同 由癌细胞选择来促进肿瘤的启动和进展，并将这一知识应用于 开发新的治疗方法。在过去的50年里，强大的基础科学 该计划项目的基金会使成员能够识别癌症的脆弱性并开发新的 和高度具体的治疗策略。该计划继续采取多管齐下的方式 在基础癌症研究中，以识别和破坏癌症潜在的分子依赖性。 在该计划内，有三个高度整合的项目(以致癌转录因子为目标；RNA 癌症中的剪接失调；作为癌症驱动因素和依赖性的调控RNA)和四个创新 正在使用尖端技术研究癌症生物学分子机制的核心。要实现 该计划的目标是，这些研究将利用人类癌症的新有机模型，开创成像的先河 动物模型中的模式，针对其他不可用药的治疗性反义寡核苷酸策略 生物化学、细胞生物学和分子生物学的目标和前沿方法。研究人员将 询问两种最具破坏性的肿瘤类型的基础，乳腺癌和基底细胞样癌 胰腺。所有这些工作都由四个核心支持，这些核心提供对技术、服务和专业知识的访问 所有这些都结合在一起，提高了生产率，促进了互动。 本计划的互动性和协作性为每个项目提供了指导，使其超越了单一项目 潜力。所有三个项目的研究都涉及重叠的主题和受益于 其他计划成员。总而言之，该计划正在朝着其确定 新的治疗目标将对癌症治疗产生重大影响。

OVERALL PROJECT SUMMARY The overall goal of this Program is to understand how transcription and splicing regulation is altered and co- opted by cancer cells to promote tumor initiation and progression, and to apply this knowledge towards development of new therapeutic approaches. During the past 50 years, the strong underlying basic science foundation of the Program Project has allowed members to identify vulnerabilities in cancer and develop novel and highly specific therapeutic strategies. This Program continues to take a multi-pronged approach grounded in basic cancer research to identify and disrupt the molecular dependencies underlying cancer. Within this Program, there are three highly integrated Projects (Targeting oncogenic transcription factors; RNA Splicing dysregulation in cancer; Regulatory RNAs as cancer drivers and dependencies) and four innovative Cores that are using cutting edge technologies to study the molecular mechanisms of cancer biology. To achieve the Program's goals, these studies will exploit novel organoid models of human cancers, pioneering imaging modalities in animal models, therapeutic antisense oligonucleotide strategies against otherwise undruggable targets, and cutting-edge methods in biochemistry, cell biology and molecular biology. The researchers will interrogate the basis of two of the most devastating types of tumors, basal-like carcinomas of the breast and pancreas. All of this work is supported by four Cores that provide access to technologies, services, and expertise that all combine to enhance productivity and promote interactions. The interactive and collaborative nature of this Program guides each of these Projects beyond their singular potential. Research in all three Projects touches on overlapping themes and benefits from the expertise of the other Program members. Together, this Program is making significant progress towards its goal of identifying novel therapeutic targets that will substantially impact cancer treatment.