Establishment of an ex vivo precision-cut lung slice model for the evaluation of drug-radiation responses

体外精密切割肺切片模型的建立用于评估药物辐射反应

• 批准号: 1963111
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1963111
• 关键词: Establishment; ex; vivo; precision; cut

Our research focuses on lung cancer where our primary aim is to identify new drug targets and to determine how best to integrate novel therapies with current standards of care in lung cancer, and to optimise combination treatments including radiation therapy.During its development, lung cancer acquires activating mutations that are critical for continued tumour growth. For example, recurrent mutations have been described in several key oncogenes (including EGFR, KRAS, ALK, BRAF, PIK3CA and ERBB2). Since these activating mutations are not found in normal tissues, we are currently screening for combinations of novel compounds that can selectively kill these cells while leaving normal cells unaffected.Importantly, lung cancer can also acquire loss of function mutations in tumour suppressor genes. As a consequence, tumour cells can become highly dependent on compensatory signalling pathways, which might then be targeted in order to kill the tumour cells. In contrast, non-tumour cells without the tumour suppressor gene mutation, are less dependent on these compensatory pathways and therefore are relatively unaffected by pathway inhibition. We are currently screening for targets and compounds that can lead to selective killing of cells with tumour suppressor gene mutations that are common in lung cancer (e.g. TP53, LKB1, ATM).

我们的研究重点是肺癌，我们的主要目标是确定新的药物靶点，并确定如何最好地将新疗法与肺癌的当前护理标准相结合，并优化包括放射治疗在内的联合治疗。在其发展过程中，肺癌获得了对肿瘤持续生长至关重要的激活突变。例如，在几种关键癌基因（包括EGFR、KRAS、ALK、BRAF、PIK3CA和ERBB2）中描述了复发性突变。由于这些激活突变在正常组织中没有发现，我们目前正在筛选新化合物的组合，这些化合物可以选择性地杀死这些细胞，而不影响正常细胞。重要的是，肺癌也可以获得肿瘤抑制基因的功能丧失突变。因此，肿瘤细胞可以变得高度依赖于补偿信号通路，然后可以靶向这些通路以杀死肿瘤细胞。相反，没有肿瘤抑制基因突变的非肿瘤细胞较少依赖于这些代偿途径，因此相对不受途径抑制的影响。我们目前正在筛选可以选择性杀死肺癌中常见的肿瘤抑制基因突变（例如TP53，LKB 1，ATM）细胞的靶点和化合物。