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

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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.