基因缺陷可能阻止细胞对DNA的损伤

美国的一项新研究结果揭示，在一种脑肿瘤中经常发现的基因缺陷可能阻止细胞对DNA的损伤。

耶鲁大学的研究人员发现，这个缺陷引起实验室的脑肿瘤细胞对治疗一些卵巢癌女性的药物变得高度的敏感。

根据资深作者Ranjit Bindra博士，这项发现 - 如果在临床试验中得到证实 - 可能有“实践变化的影响”，因为它表明治疗某些脑肿瘤一种可能的新方法。

该研究发表在《科学转化医学》的期刊上，调查了两个称为IDH1和IDH2基因的缺陷。这些已经在称为神经胶质瘤的一组脑肿瘤中发现，伴随着几种其他类型的癌症，包括黑素瘤。

研究团队调查研究一个盘子里的细胞，发现这些基因的缺陷能够阻止细胞修复对它们DNA的损害。

然后，研究人员在细胞上测试了许多不同的药物，发现它们被称为属于PARP抑制剂种类的药物杀死。这些药物利用细胞的DNA修复机制的缺陷，并已经用于治疗卵巢癌的一些病例。

研究团队通过实验室和老鼠研究患者的胶质瘤细胞来佐证这些研究成果，隐藏着错误的基因。他们发现肿瘤对一种称为olaparib（Lynparza）的PARP抑制剂特别敏感。

    英国癌症研究院的脑肿瘤专家Anthony Chalmers教授把这个结果描述为“非常的重要”和可能“彻底变革胶质瘤的治疗方式”。

   “PARP抑制剂有非常少的副作用，并且能够用来治疗这些脑肿瘤的前景是非常令人兴奋的，”他补充道。

“在这个研究中基因缺陷在生长较慢的胶质瘤中尤其普通，但在生长较快的胶质母细胞瘤发现有10%。所以，可能从这些药物中受益的患者数量相当高”。

   “因为对于这些脑肿瘤的治疗方式经常不是很有效，非常高兴有一些具有潜力的替代方法。”

    该团队正在设计一个临床试验来测试像olaparib类似的药物是否可用于治疗其肿瘤有IDH基因错误的患者。

Ovarian cancer drug could target gene fault in brain tumours

    A genetic flaw that’s often found in a type of brain tumour may stop the cells from fixing damage to their DNA, findings from a new US study suggest.

    Researchers at Yale found that this weakness caused brain tumour cells in the lab to become highly sensitive to a drug that’s  used to treat some women with ovarian cancer.

    According to senior author Dr Ranjit Bindra, the discovery – if confirmed in clinical trials – could have “practice-changing implications” as it suggests a possible new approach to treating certain brain tumours.

Published in the journal Science Translational Medicine(link is external), the study looked at faults in two genes called IDH1 and IDH2. These have been found in a group of brain tumours called gliomas, alongside several other types of cancer, including melanoma.

    Looking at cells in a dish, the team found that mistakes in these genes prevented the cells from being able to repair damage to their DNA.

The researchers then tested a number of different drugs on the cells, discovering that they were killed by drugs belonging to a group known as PARP inhibitors.    These drugs exploit weaknesses in cells’ DNA repair machinery, and are already used to treat some cases of ovarian cancer.

    The team backed up these findings by looking at glioma cells from patients in the lab and in mice, which harboured the faulty genes. They found that the tumours were particularly sensitive to a type of PARP inhibitor called olaparib (Lynparza).

Professor Anthony Chalmers, a Cancer Research UK expert on brain tumours, described the results as “hugely important” and could “revolutionise the treatment of gliomas”.

    “PARP inhibitors have very few side effects and the prospect of being able to use them to treat these brain tumours is very exciting,” he added.

   “The genetic faults investigated in this study are extremely common in slower-growing gliomas but are also found in up to 10% of faster-growing glioblastomas, so the number of patients who might benefit from these drugs is quite high.”

   “Since the treatments we have aren’t always effective for these brain tumours, it’s great to have some promising alternatives.”

    The team is now designing a clinical trial to test whether drugs like olaparib could be used to treat patients whose tumours have mistakes in their IDH genes.

媒体链接：基因缺陷可能阻止细胞对DNA的损伤