Development and technical evaluation of first in class small molecule inhibitors for the treatment of brain tumours

治疗脑肿瘤的一流小分子抑制剂的开发和技术评估

• 批准号: 10037882
• 金额: $ 55.08万
• 依托单位: PATHIOS THERAPEUTICS LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10037882
• 关键词: Development; technical; evaluation; first; class

**Pathios Therapeutics** specialise in identifying and developing molecules that alter the signalling of a specialised cell-surface receptor in the immune system that detects changes in the local pH called GPR65\. Pathios has a deep understanding of GPR65 and develop drugs that block or 'switch off' the signalling of this receptor to treat cancers.Pathios in collaboration with the University of Nottingham wish to capitalise on its expertise around GPR65 to develop drugs that can treat malignant brain tumours. The annual cost to the UK taxpayer of brain tumours is almost £0.6Bn. Current treatments are woefully inadequate and accompanied by debilitating side effects. Around 12,000 people a year are diagnosed with a malignant brain tumour in the UK, with this type of cancer causing ~5,000 annual deaths. People with the most severe type of brain tumour, glioblastoma-multiforme (GBM), typically only survive 15-16 months. Most brain cancer patients will receive surgery combined with radiotherapy and/or chemotherapy (c.£180,000/patient). However, treatment is rarely curative.Pathios' approach to treating cancer is based on recent ground-breaking research showing that activation of the GPR65 receptor by the acidic microenvironment that is typical of many tumours leads to the disarming of specialized cells in the innate immune system called tumour associated macrophages (TAMs). This prevents these cells from being able to attack the cancer and stimulate other types of immune cells called T-cells. By 'switching off' GPR65, Pathios' drugs will be able to restore the ability of TAMs to destroy cancer cells and stimulate an effective immune response.Across all human tumour types, the levels of the GPR65 receptor are higher in malignant brain tumours than in any other type of cancer. Brain tumours are also highly infiltrated by TAMs and are characterized by a highly acidic local microenvironment. Brain tumours would therefore appear to be especially amenable to an approach that seeks to suppress GPR65 signalling. In contrast to Pathios's therapies for other forms of cancer, a treatment for brain tumours would need to have special properties that enable it to enter the central nervous system (CNS). Pathios has identified a series of molecules with such properties and now seeks to optimise these further. Alongside this, Pathios will work with the world class Centre for Cancer Sciences (CCS) at the University of Nottingham to create the state-of-the-art tools required to demonstrate that these molecules will be effective against human brain tumours.

**Pathios Therapeutics** 专注于识别和开发分子，这些分子可以改变免疫系统中一种专门的细胞表面受体的信号传导，该受体可以检测局部pH值的变化，称为GPR 65\。Pathios对GPR 65有着深刻的理解，并开发了阻断或“关闭”该受体信号传导的药物来治疗癌症。Pathios与诺丁汉大学合作，希望利用其在GPR 65方面的专业知识开发治疗恶性脑肿瘤的药物。英国纳税人每年因脑肿瘤而花费的费用几乎为6亿英镑。目前的治疗方法严重不足，并伴有使人衰弱的副作用。在英国，每年约有12，000人被诊断患有恶性脑瘤，这种类型的癌症每年导致约5，000人死亡。患有最严重类型的脑肿瘤，多形性胶质母细胞瘤（GBM）的人通常只能存活15-16个月。大多数脑癌患者将接受手术联合放疗和/或化疗（约180，000英镑/患者）。Pathios治疗癌症的方法是基于最近的突破性研究，该研究表明，GPR 65受体被许多肿瘤典型的酸性微环境激活，导致先天免疫系统中称为肿瘤相关巨噬细胞（TAM）的特化细胞解除武装。这可以防止这些细胞攻击癌症并刺激其他类型的免疫细胞，称为T细胞。通过“关闭”GPR 65，Pathios的药物将能够恢复TAM破坏癌细胞的能力，并刺激有效的免疫反应。在所有人类肿瘤类型中，恶性脑肿瘤中的GPR 65受体水平高于任何其他类型的癌症。脑肿瘤也被TAM高度浸润，并且以高度酸性的局部微环境为特征。因此，脑肿瘤似乎特别适合于寻求抑制GPR 65信号传导的方法。与Pathios对其他形式癌症的治疗相反，脑肿瘤的治疗需要具有特殊的特性，使其能够进入中枢神经系统（CNS）。Pathios已经确定了一系列具有这些特性的分子，现在正在寻求进一步优化这些分子。除此之外，Pathios还将与诺丁汉大学世界级的癌症科学中心（CCS）合作，创造最先进的工具，以证明这些分子对人类脑肿瘤有效。