Identifying deubiquitylating enzymes (DUBs) as targets for treating of platinum-resistant ovarian cancer

为治疗铂耐药卵巢癌量身定制的新疗法是一个明显未满足需求的领域。卵巢癌每年造成的死亡人数超过任何其他女性生殖系统癌症，耐药性的发展仍然是目前化疗的主要限制。我们提出了一种创新的方法来确定耐药卵巢癌的新药物靶点，这种方法将利用导致耐药的肿瘤中的变化。我们建议通过筛选所有已知的人类去泛素化酶（DUBs）——一种新型的、可药物化的酶——来确定创新靶点，其抑制将选择性地杀死或重新致敏耐药卵巢肿瘤。然后，经过验证的最佳靶点将进入MISSION Therapeutics Ltd的管道，进行进一步的药物发现工作，以期将新的、创新的和有效的化疗药物进入临床。

Novel therapies tailored for treatment of platinum-resistant ovarian cancer is an area of clear unmet need. Ovarian cancer is responsible for more deaths per year than any other cancer of the female reproductive system and developing drug resistance remains the main limitation of current chemotherapies. We propose an innovative approach to identifying novel drug targets for drug-resistant ovarian cancer that would exploit the very changes in the tumour that have led to the resistance. We propose to do this by screening all known human deubiquitylases (DUBs) – a novel, druggable class of enzymes – to identify innovative targets whose inhibition would selectively kill or re-sensitise drug-resistant ovarian tumours. The best validated targets will then enter the MISSION Therapeutics Ltd pipeline for further drug discovery efforts with a view to new, innovative and effective chemotherapies entering the clinic.