Assessing new therapeutic opportunities linked to TCR signalling in mature T-cell lymphomas with unmet need

评估与未满足需求的成熟 T 细胞淋巴瘤中 TCR 信号传导相关的新治疗机会

• 批准号: MR/P028160/1
• 负责人: Matilda Katan
• 金额: $ 78.68万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FP028160%2F1
• 关键词: Assessing; new; therapeutic; opportunities; linked

Knowledge about the specific molecular and genetic makeup of a patient's tumour provides valuable guide for diagnosis and for decisions about the treatment. This approach, described as personalized or precision medicine, has recognized benefits for patients, drug development and healthcare. However, linking information that describes genetic aberrations in tumours with successful new treatments requires considerable research effort. In this proposal we outline our plan to assess new potential drug targets in T-cell lymphomas where patient's outcome with current treatments remains bleak and where recent genetic studies highlighted changes that could be linked to cancer development. We will combine expertise in a close collabariton that we believe is necessary to provide definitive supporting evidence. This expertise covers long standing involvement in studies of the development of particular forms of T-cell lymphomas and an extensive expertise and contribution to structural and mechanistic understanding of potential targets which will both facilitate ongoing efforts in drug development. This will bring together in-depth insights from studies of isolated proteins, findings from the analysis of cells from actual patient's tumours and initial generation and characterization of potential drugs, all using the latest methodological advances in respective research areas. If confirmed as feasible, the new treatment options will have a wider relevance, including some other cancer types, drug-resistance in specific cancers and a range of immune disorders.

关于患者肿瘤的特定分子和遗传组成的知识为诊断和治疗决策提供了有价值的指导。这种方法被称为个性化或精准医疗，已被公认为对患者、药物开发和医疗保健有益。然而，将描述肿瘤遗传畸变的信息与成功的新治疗方法联系起来需要大量的研究工作。在这项提案中，我们概述了我们评估T细胞淋巴瘤新的潜在药物靶点的计划，其中患者目前治疗的结果仍然暗淡，最近的遗传研究突出了可能与癌症发展有关的变化。我们将联合收割机的专业知识结合在一起，密切合作，我们认为这是必要的，以提供明确的支持证据。这种专业知识包括长期参与特定形式的T细胞淋巴瘤的发展研究，以及对潜在靶点的结构和机制理解的广泛专业知识和贡献，这两者都将促进药物开发的持续努力。这将汇集来自分离蛋白质研究的深入见解，来自实际患者肿瘤细胞分析的发现以及潜在药物的初始生成和表征，所有这些都使用各自研究领域的最新方法学进展。如果证实可行，新的治疗选择将具有更广泛的相关性，包括其他一些癌症类型，特定癌症的耐药性和一系列免疫疾病。

项目成果

Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane.

• DOI: 10.1042/ebc20200041
• 发表时间: 2020-09-23
• 期刊: Essays in biochemistry
• 影响因子: 6.4
• 作者: Katan M;Cockcroft S
• 通讯作者: Cockcroft S

Cells of the human intestinal tract mapped across space and time.

• DOI: 10.1038/s41586-021-03852-1
• 发表时间: 2021-09
• 期刊: Nature
• 影响因子: 64.8
• 作者: Elmentaite R;Kumasaka N;Roberts K;Fleming A;Dann E;King HW;Kleshchevnikov V;Dabrowska M;Pritchard S;Bolt L;Vieira SF;Mamanova L;Huang N;Perrone F;Goh Kai'En I;Lisgo SN;Katan M;Leonard S;Oliver TRW;Hook CE;Nayak K;Campos LS;Domínguez Conde C;Stephenson E;Engelbert J;Botting RA;Polanski K;van Dongen S;Patel M;Morgan MD;Marioni JC;Bayraktar OA;Meyer KB;He X;Barker RA;Uhlig HH;Mahbubani KT;Saeb-Parsy K;Zilbauer M;Clatworthy MR;Haniffa M;James KR;Teichmann SA
• 通讯作者: Teichmann SA

Severe Autoinflammatory Manifestations and Antibody Deficiency Due to Novel Hypermorphic PLCG2 Mutations.

• DOI: 10.1007/s10875-020-00794-7
• 发表时间: 2020-10
• 期刊: Journal of clinical immunology
• 影响因子: 9.1
• 作者: Martín-Nalda A;Fortuny C;Rey L;Bunney TD;Alsina L;Esteve-Solé A;Bull D;Anton MC;Basagaña M;Casals F;Deyá A;García-Prat M;Gimeno R;Juan M;Martinez-Banaclocha H;Martinez-Garcia JJ;Mensa-Vilaró A;Rabionet R;Martin-Begue N;Rudilla F;Yagüe J;Estivill X;García-Patos V;Pujol RM;Soler-Palacín P;Katan M;Pelegrín P;Colobran R;Vicente A;Arostegui JI
• 通讯作者: Arostegui JI