Targeting the Salt Inducible Kinase 2 (SIK2) for cancer therapy

靶向盐诱导激酶 2 (SIK2) 进行癌症治疗

• 批准号: MR/M025381/1
• 负责人: Heather McKinnon
• 金额: $ 197.96万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM025381%2F1
• 关键词: Targeting; Salt; Inducible; Kinase; SIK2

Approximately 200000 women worldwide are diagnosed with ovarian cancer of which around 7000 are in the UK. Early diagnosis is difficult and as a result 90% of those diagnosed have cancer which has spread beyond the ovaries. The standard care for patients involves surgery and chemotherapy and though the initial response to treatment is good, the majority of patients suffer from recurrence. Indeed the 5-year survival for women with advanced stage ovarian cancer is approximately 30%.One of the main reasons for recurrence is that surgery is unable to remove 100% of the cancer cells and these can form the basis for the cancer to return and to spread to specific areas local to the original tumour. These local areas are rich in fat cells called adipocytes and there are factors in ovarian cancer cells which promote cancer growth in these adipocyte regions. We have identified one of these factors, a protein called Salt Inducible Kinase 2 or SIK2. We have evidence that reducing SIK2 levels in cell lines derived from human tumours reduces their proliferation and may stop them spreading in patients. We will try to identify a small molecule inhibitor of the SIK2 enzyme which can be used either alone or in conjunction with the current standard of care to help improve survival rates for women with ovarian cancer.

全世界约有200000名妇女被诊断出患有卵巢癌，其中约7,000人在英国。早期诊断很困难，因此90%的确诊患者患上了已经扩散到卵巢以外的癌症。对患者的标准护理包括手术和化疗，尽管最初的治疗反应良好，但大多数患者会复发。事实上，晚期卵巢癌患者的5年生存率约为30%。复发的主要原因之一是手术无法100%切除癌细胞，这些癌细胞可以形成癌症复发的基础，并扩散到原始肿瘤的特定区域。这些区域富含被称为脂肪细胞的脂肪细胞，卵巢癌细胞中存在促进这些脂肪细胞区域癌细胞生长的因素。我们已经确定了其中一个因素，一种名为盐诱导蛋白2或SIK2的蛋白质。我们有证据表明，降低来自人类肿瘤的细胞系中SIK2的水平可以减少它们的增殖，并可能阻止它们在患者中传播。我们将尝试确定一种SIK2酶的小分子抑制剂，它可以单独使用，也可以与当前的护理标准一起使用，以帮助提高卵巢癌女性患者的存活率。