Overcoming treatment resistance in glioblastoma multiforme by tumour specific inhibition of DNA repair.

目前，大多数恶性脑肿瘤对治疗有抗药性，患者平均只能活一年。我们研究的目的是通过增加放疗和化疗对肿瘤的影响而不增加对健康组织的损害来提高这些患者的预期寿命。我们以前的PARP抑制剂药物研究很有希望，我们已经计划进行临床试验，看看患者是否受益。该项目的一个目的是确定哪些患者受益于PARP抑制剂，并了解原因。我们还将研究PARP抑制剂是否增加放疗根除可能导致大多数肿瘤复发的细胞的能力。如果PARP抑制剂无效，我们将测试其他影响细胞对放疗反应的药物。最后，我们将研究一种可能的新疗法，用于治疗一种对化疗极其耐药的脑肿瘤。这种新的治疗方法似乎可以降低一种名为MGMT的蛋白质的水平，这种蛋白质可以保护肿瘤细胞免受化疗的影响。我们需要证明这种新药能增加对脑肿瘤细胞的杀伤力，而不会对健康组织造成额外的损害。

At the moment, most malignant brain tumours are resistant to treatment and patients live for an average of only one year. The aim of our research is to improve life expectancy for these patients by increasing the effects of radiotherapy and chemotherapy on the tumours without increasing damage to healthy tissues. Our previous work with drugs called PARP inhibitors has been promising, and we have planned a clinical trial to see if patients benefit. One aim of this project is to identify which patients benefit from PARP inhibitors, and to understand why. We will also investigate whether PARP inhibitors increase the ability of radiotherapy to eradicate the cells that are probably responsible for most cases of tumour recurrence. If PARP inhibitors are not effective we will test other drugs that affect the way cells respond to radiotherapy. Finally, we will investigate a possible new treatment for a type of brain tumour that is extremely resistant to chemotherapy. The new treatment appears to reduce levels of a protein called MGMT which otherwise protects tumour cells from chemotherapy. We need to show that the new drug increases killing of brain tumour cells without causing extra damage to healthy tissues.