Translational Development of a novel therapy for Malignant Mesothelioma

据估计，英国有250万人患有癌症，预计到2030年将增加到400万。许多癌症的治疗方法和结果都有所改善，但对于恶性间皮瘤（MM）等罕见的侵袭性癌症却没有改善。MM是一种无法治愈的肺部和胸部（胸膜）或腹腔（腹膜）的癌症，通常由接触石棉纤维引起。尽管进行了多模式治疗（化疗、放疗和手术），MM仍被认为是终末期疾病，中位生存期仅为14.8个月。只有不到5%的患者能存活5年或更长时间，这是所有癌症中生存率最差的一种。只有两种化疗药物可能适用，患者通常会对它们产生耐药性。在过去的10年里，由伍尔弗汉普顿大学的王伟光教授领导的一个多学科科学团队研究并证明了双硫仑（DS），一种60多年来用于治疗数百万酗酒患者的常规药物，对MM具有出色的活性。虽然DS在实验室中效果良好，但在临床试验中从未证明令人满意。这主要是由于DS在血液中的半衰期极短（< 4分钟）。王教授已经找到了一种方法，将这种药物包裹在PLGA聚合物微颗粒中，保护DS在体内不被降解，并控制其释放。在患有癌症的老鼠身上进行测试时，这种胶囊化药物已经取得了令人鼓舞的研究结果。该项目的目的是对疗效和作用机制进行必要的评估，以便团队可以进行临床试验。该项目的合作团队——diulfican、Pharmidex制药服务公司和伍尔弗汉普顿大学——在开发这种新疗法的初始阶段已经成功合作过。diulfican是2018年从伍尔弗汉普顿大学分拆出来的一家公司，拥有与封装DS相关的专利和其他知识产权，现在专注于将这种疗法推向临床。合作伙伴将重点放在间皮瘤上，因为这种疾病是一种“孤儿病”，因为它很罕见，而且没有任何非常有效的治疗方法。英国监管机构MHRA为治疗指定孤儿疾病的治疗提供费用和程序方面的帮助，这意味着减少了患者获得药物批准的成本和时间。

There are an estimated 2.5 million people living with cancer in the UK, projected to increase up to 4 million by 2030\. Treatments and the outcomes for many cancers have improved, but not for rare, aggressive cancers such as Malignant Mesothelioma (MM). MM is an incurable cancer of the lining of the lung and chest (pleura) or abdominal cavity (peritoneum), typically caused by exposure to asbestos fibres. Despite multimodal treatment (chemotherapy, radiotherapy and surgery), MM is regarded as a terminal condition with a median survival of just 14.8 months. Fewer than 5% of patients survive for 5 years or more, representing one of the worst survival rates among all cancers. Only 2 chemotherapy drugs are potentially applicable and patients normally develop resistance to them.Over the last 10 years, a multidisciplinary scientific team led by Professor Weiguang Wang at the University of Wolverhampton have researched and demonstrated that Disulfiram (DS), a drug used routinely for the treatment of alcoholism in millions of patients over more than 60 years, has excellent activity against MM. Whilst DS works well in the laboratory, it has never proven satisfactory in clinical trials. This is mainly due to the extremely short half-life of DS in the bloodstream (< 4 min). Professor Wang has found a way of encapsulating the drug in PLGA polymeric micro particles that protects the DS from degradation in the body and controls its release. Promising research results have been achieved for the encapsulated drug when tested in mice with cancer. The aim of this project is to carry out the necessary evaluation of efficacy and mechanism of action so that the team can progress towards clinical trials.The collaborating team on the project -- Disulfican, Pharmidex Pharmaceutical Services and the University of Wolverhampton -- have successfully worked together before, in the initial stages of developing this new therapy. Disulfican was created as a spin-out company from the University of Wolverhampton in 2018, owns the patents and other intellectual property related to encapsulated DS, and is now focussed on advancing this therapy into clinic.The partners focussed on mesothelioma because this condition is an 'orphan disease', due to its rarity and the absence of any very effective treatments. The UK regulator MHRA gives assistance with fees and procedures for therapies to address designated orphan diseases which means that the costs and timescales to get the drug approved for patients is reduced.