Commercialising the Next Generation of Synthetic Lethality: preclinical validation of lead drug-targets and discovery platform

**背景：**胶质瘤是世界上最常见的脑癌类型。它们影响成人和儿童，每年在全球造成227,000人死亡。95%的高级别病例在死亡前会出现癫痫、头痛、呕吐、失明和性格改变等症状。除了可怕的人力成本，神经胶质瘤给英国经济带来的负担每年超过10亿英镑，其中包括国民医疗服务体系（NHS）的成本、社会保健和病假费用。如今，神经胶质瘤的治疗包括手术后的放疗和化疗。然而，尽管进行了积极的治疗，胶质瘤仍然几乎是普遍致命的，并且在过去的15年里没有开发出新的药物。一个主要的问题是，神经胶质瘤倾向于进化出对药物的耐药性，因此复发是常见的。**创新：****CoSyne Therapeutics**是一家总部位于伦敦的精准医疗公司。我们的目标是彻底改变我们治疗脑癌的方式。我们是从伦敦帝国理工学院分拆出来的，建立在该领域多年的学术研究基础上。我们创新的核心是我们最先进的计算平台，它利用机器学习来寻找治疗癌症的新方法。我们的平台能够识别脑肿瘤的遗传特征，这些特征使它们容易受到抑制基因药物的影响。然后，我们可以利用这些信息开发针对每个患者特定脑肿瘤的新药。我们的技术有可能克服神经胶质瘤的耐药性问题，并可能导致一种针对脑肿瘤的新型精确药物。我们的技术也可以扩展到神经胶质瘤以外的其他癌症，因此有可能产生许多对抗癌症的新药。**项目：**有了Innovate UK的资助，我们将通过展示我们的技术可以成功治疗小鼠脑癌来验证我们的计算平台和我们最有希望的药物靶点。对于我们公司来说，这将是一个改变游戏规则的里程碑，并将吸引大量投资，使我们能够开发新药并将其推进临床试验。**我们的愿景：**今天，患者在手术切除肿瘤后接受非靶向化疗。我们设想未来病人在手术后对他们的肿瘤进行基因测序，以确定每个肿瘤中存在的确切基因。然后根据肿瘤的特定基因组成选择精准药物。因此，每位患者都将接受针对其癌症分子/基因特征量身定制的药物。因此，这个项目将使我们更接近实现用精准药物治疗癌症的目标。

**Background:**Gliomas are the commonest type of brain-cancer worldwide. They affect adults as well as children and cause **227,000 deaths** globally every year. Patients suffer with seizures, headaches, vomiting, blindness and personality-changes before **death follows in 95%** of high-grade cases. In addition to the terrible human cost, the burden of gliomas on the UK economy is over **£1billion/year** in NHS costs, social-care and sick-leave expenses.Today, glioma treatment involves surgery followed by radiotherapy and chemotherapy. However, despite aggressive treatment, gliomas are still almost universally fatal and no new drugs have been developed in over 15 years. A major problem is that glioma tumours tend to evolve resistance to drugs and so relapses are common.**Innovation:****CoSyne Therapeutics** is a precision-medicine company based in London. Our goal is to revolutionise the way we treat brain-cancers. We are a spin-out from Imperial College London and are building on many years of academic research in the field.The heart of our innovation is our state-of-the-art computational platform, which utilises machine-learning to find new ways to treat cancer. Our platform is able to identify genetic features in brain tumours that make them vulnerable to drugs that inhibit genes. We can then use this information to develop new drugs tailored to each individual patient's specific brain tumour.Our technology has the potential to overcome the problem of drug-resistance in gliomas and could lead to a new class of precision-drugs against brain tumours. Our technology can also be scaled to other cancers beyond gliomas, and so has the potential to generate many new drugs in the fight against cancer.**Project:**With this Innovate UK grant, we will validate our computational platform and our most promising drug-targets by showing that our technology can successfully treat brain-cancers in mice. This would be a game-changing milestone for our company and would attract considerable investment to allow us to create new drugs and progress them to clinical trials.**Our vision:**Today, patients receive non-targeted chemotherapy after they have their tumours surgically removed. We envisage a future whereby patients have their tumours genetically-sequenced after surgery to identify the exact genes present in each tumour. Precision drugs would then be selected based on the specific genetic-makeup of that tumour. Each patient would thus receive a drug tailored to the exact molecular/genetic features of their cancer. This project will therefore bring us significantly closer to realising this goal of curing cancers with precision-drugs.