A BMI1/CHD7 signature in medulloblastoma with poor prognosis.

髓母细胞瘤中的 BMI1/CHD7 特征预后不良。

• 批准号: MR/N000528/1
• 负责人: Silvia Marino
• 金额: $ 81.06万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN000528%2F1
• 关键词: BMI1; CHD7; signature; medulloblastoma; poor

Brain tumours account for a large proportion of childhood tumours. Medulloblastomas are the most common brain cancers seen in young children. They are malignant tumours formed from poorly developed cells at a very early stage of their life. They develop in a region at the back of the head called the posterior fossa in the region of the brain called the cerebellum, but may spread to other parts of the brain. Very rarely, medulloblastomas may spread to other parts of the body. The main treatments available to children with medulloblastomas today are surgery, radiotherapy or chemotherapy. These treatments can be effective and kill the tumour cells in a proportion of patients; however they almost invariably also result in severe side effects which are particularly damaging in young children as the brain is still growing. These side effects mainly affect a child's physical and intellectual development with hearing and visual disturbances, growth and hormonal changes, reduced fertility, behavioural changes, learning problems, difficulties with coordination and secondary cancers. A report recently compiled by the New Philanthropy Capital, has identified brain tumours as one of the worst funded cancer, the cumulative research spend on brain tumours between 2002 and 2011 was less than 1% of all NCRI research spend. We have recently employed powerful new genetic approaches to identify specific molecular changes that characterize a particularly aggressive subtype of medulloblastomas for which no specific treatment exists. We have established cells from these tumours that can be grown in the laboratory and we have the ability to produce mice that develop the same types of tumours. We will use state-of-the-art methods to study the mechanisms responsible for the formation and growth of these tumours. These studies will lead to the identification of new genes and pathways that can be targeted to stop or reduce tumour formation and growth. We will target these genes and pathways to identify the ones that show most promise as therapeutic targets, which will represent the first important steps towards developing effective, new generation treatments for one of the most aggressive subtypes of this devastating disease.

脑肿瘤占儿童肿瘤的很大比例。髓母细胞瘤是最常见的脑肿瘤，见于幼儿。它们是由发育不良的细胞在生命的早期阶段形成的恶性肿瘤。它们发生在后脑勺的一个区域，称为小脑的后颅窝，但可能会扩散到大脑的其他部位。极少数情况下，髓母细胞瘤可能会扩散到身体的其他部位。目前，儿童髓母细胞瘤的主要治疗方法是手术、放疗或化疗。这些治疗可以有效地杀死一部分患者的肿瘤细胞;然而，它们几乎总是会导致严重的副作用，这对大脑仍在生长的幼儿特别有害。这些副作用主要影响儿童的身体和智力发育，包括听力和视力障碍、生长和荷尔蒙变化、生育能力下降、行为变化、学习问题、协调困难和继发性癌症。新慈善资本最近编制的一份报告将脑肿瘤确定为资助最差的癌症之一，2002年至2011年期间脑肿瘤的累积研究支出不到NCRI所有研究支出的1%。我们最近采用了强大的新的遗传学方法，以确定特定的分子变化，其特征是一个特别积极的髓母细胞瘤亚型，没有具体的治疗存在。我们已经从这些肿瘤中建立了可以在实验室中生长的细胞，并且我们有能力生产出发展相同类型肿瘤的小鼠。我们将使用最先进的方法来研究这些肿瘤形成和生长的机制。这些研究将导致识别新的基因和途径，可以有针对性地阻止或减少肿瘤的形成和生长。我们将针对这些基因和途径，以确定最有希望作为治疗靶点的基因和途径，这将代表为这种毁灭性疾病的最具侵略性的亚型之一开发有效的新一代治疗方法的第一个重要步骤。

项目成果

Combination of BMI1 and MAPK/ERK inhibitors is effective in medulloblastoma.

• DOI: 10.1093/neuonc/noac052
• 发表时间: 2022-08-01
• 期刊: Neuro-oncology
• 影响因子: 15.9

TAp73 is a marker of glutamine addiction in medulloblastoma.

• DOI: 10.1101/gad.302349.117
• 发表时间: 2017-09-01
• 期刊: Genes & development
• 影响因子: 10.5
• 作者: Niklison-Chirou MV;Erngren I;Engskog M;Haglöf J;Picard D;Remke M;McPolin PHR;Selby M;Williamson D;Clifford SC;Michod D;Hadjiandreou M;Arvidsson T;Pettersson C;Melino G;Marino S
• 通讯作者: Marino S

Inositol treatment inhibits medulloblastoma through suppression of epigenetic-driven metabolic adaptation.

• DOI: 10.1038/s41467-021-22379-7
• 发表时间: 2021-04-12
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Badodi S;Pomella N;Zhang X;Rosser G;Whittingham J;Niklison-Chirou MV;Lim YM;Brandner S;Morrison G;Pollard SM;Bennett CD;Clifford SC;Peet A;Basson MA;Marino S
• 通讯作者: Marino S

Convergence of BMI1 and CHD7 on ERK Signaling in Medulloblastoma.

• DOI: 10.1016/j.celrep.2017.11.021
• 发表时间: 2017-12-05
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Badodi S;Dubuc A;Zhang X;Rosser G;Da Cunha Jaeger M;Kameda-Smith MM;Morrissy AS;Guilhamon P;Suetterlin P;Li XN;Guglielmi L;Merve A;Farooq H;Lupien M;Singh SK;Basson MA;Taylor MD;Marino S
• 通讯作者: Marino S