Development of tumour specific radiation sensitising treatments

放射治疗(RT)在许多实体肿瘤的治疗中起着关键作用，它涉及到将高能X射线精确地输送到局部肿瘤。在治疗环境中，治疗可以单独使用，也可以与化疗或免疫治疗结合使用。尽管技术进步使立体定向消融体放射治疗(SABR)等新型、高效的RT治疗成为可能，但没有一种方法能够完全避免健康组织接受某些放射治疗，这往往会导致显著的副作用。因此，仅仅通过增加给药剂量来获得更好的肿瘤控制并不是一个适当的解决方案。一种更容易处理的方法是开发有选择地使肿瘤对辐射更敏感的治疗方法，而不对正常组织产生影响。我们之前已经进行了高通量化合物和基因筛查，以确定新的、临床上可翻译的靶点。这导致了几种新化合物的开发，我们预计这些化合物将导致肿瘤特异性放射增敏。该项目的目的将是对这些化合物进行深入的临床前测试，以评估它们作为临床有用治疗的适宜性。

Radiotherapy (RT) treatment plays a key role in the management of many solid tumours and involves the precise delivery of high energy X-rays to localised tumours. In the curative setting, treatment can be used alone, or in combination with chemotherapy or immunotherapy. Although technological improvements have enabled the ability to deliver novel, highly effective RT treatments such as stereotactic ablative body radiotherapy (SABR), there is no approach that is able to fully spare healthy tissues from receiving some radiotherapy, often leading to significant side-effects. Obtaining greater tumour control by simply increasing the delivered dose is therefore not an adequate solution. A more tractable approach is to develop treatments which selectively render tumours more sensitive to radiation without exerting an effect on normal tissues. We have previously conducted high-throughput compound and genetic screens to identify novel, clinically translatable targets. This has led to the development of several new compounds which we anticipate will cause tumour specific radiosensitisation. The aim of this project will be to undertake in depth pre-clinical testing of these compounds to assess their suitability as clinically useful treatments.