Identifying therapeutical opportunities within replicative stress response pathways for the development of novel therapeutic strategies

DNA损伤反应和端粒延长之间的相互作用对于基础和临床前景都很重要。端粒替代性延长（ALT）允许癌细胞通过在没有端粒酶的情况下保留其端粒来实现无限的复制潜力。10-15%的癌症使用ALT，并且与间充质和神经上皮肿瘤相关。目前，由于ALT途径的确切分子机制尚未完全了解，因此不存在用于治疗ALT依赖性肿瘤的有用疗法。该博士课程旨在研究早期分子事件，这些事件允许癌细胞启动生产性ALT依赖性端粒维持。

The interaction between DNA damage responses and telomere elongation is important for both fundamental and clinical perspectives. Alternative Lengthening of Telomeres (ALT) allows cancer cells to achieve unlimited replicative potential by preserving their telomeres in the absence of telomerase. ALT is employed by 10-15% of cancers and is associated with mesenchymal and neuroepithelial tumours. Currently, no useful therapies exist for the treatment of ALT-reliant tumours since the exact molecular mechanisms of the ALT pathway are not fully understood. This PhD programme aims to characterise the early molecular events that allow cancer cells to initiate a productive ALT-dependent telomere maintenance.