Targeting Deubiquitinases to Treat Drug-Resistant Colorectal Cancer

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Colorectal cancer (CRC) has one of the highest Worldwide incidences and mortality rates (annually \>1.3M new cases and ~610,000 deaths). Hence, there is a critical need to develop new therapeutic approaches to treat this disease, particularly in its later stages where the mortality rates are worst. Moreover, as Western populations age, this disease is going to become more prevalent placing a significant burden on our already overstretched healthcare systems.This novel academic-industrial collaboration aims to improve outcomes for patients with poor-prognosis CRC. Initially, using CRC patient cohorts, enzymes called "DUBs" that are involved in driving currently incurable disease will be identified. The plan is then to use state-of-the-art computational approaches and reagents developed by Almac Discovery to develop new drugs ("inhibitors") to target these DUBs. These new drugs will then be tested using advanced experimental models that accurately mimic the human disease.During his secondment to Almac Discovery, Longley will be the biology lead for a CRC-focussed DUB drug development programme. While the ultimate goal will be to provide new treatment options for patients currently dying from their disease, this project will also enable interactions between the Biotech Sector and Academia (one of the key goals of the scheme) as Longley will spend 60% of his time in Almac Discovery. As a senior academic, Longley will bring years of experience in cancer biology to his secondment. Moreover, by retaining a 40% academic position, this interchange will also work in reverse, with industrial best practice, knowledge and reagents flowing back into QUB. This exchange will be further enhanced by the co-location of Longley's academic lab group and Almac Discovery on the Life Sciences campus at QUB.Longley's secondment will help guide the clinical development of Almac Discovery's portfolio of DUB inhibitors. This will significantly reduce the attrition rates (a major problem in the sector) in Almac Discovery's drug discovery programmes, enhancing the attractiveness of specific programmes to 3rd party partners and investors. Since Longley has experience in drug resistance in several other cancers (lung cancer, prostate cancer, pancreatic cancer and leukaemia), he will also be able to advise Almac Discovery on the development of assets in other disease areas. Thus, this secondment will add significant value to Almac Discovery and thereby benefit the Biomedical Sciences sector of the UK economy (another key goal of the scheme).