Title: Non melanoma skin cancer from the laboratory to the clinic: Cancer Research UK Skin Tumour Laboratory
Funder: Cancer Research UK

Abstract: Background_x000D_ Keratinocyte skin cancers (KSC), including squamous cell carcinoma (cSCC) are the commonest human cancers. New effective cancer therapies and biomarkers of potentially metastatic lesions are urgently needed. The Skin Tumour Laboratory has had a longstanding interest in elucidating the molecular events that lead to the development of aggressive cSCC. We have used longitudinal clinical surveillance of major cohorts of patients with KSC to help develop and deploy skin cancer prevention strategies. High-risk patients with KSC and accelerated carcinogenesis in immuno-suppressed organ transplant recipients (OTR London) and immuno-competent patients (London and Dundee), patients with melanoma (London and Dundee) and with cSCC in genetic disease (RDEB-SCC/Dundee) underpin our translational studies, all of which are of direct relevance to cancer research._x000D_ _x000D_ Aims and objectives_x000D_ -Evaluate the contribution of (epi)genetic alterations to initiation, maintenance and progression of keratinocyte skin cancer and to evaluate functional significance of identified targets and develop tools to screen for novel drugs targeting non-melanoma skin cancer. _x000D_ -Validate developed drugs and treatments against KSC and precancers (actinic keratoses/ AK)’ and perform specific studies to elucidate treatment efficacy and disease mechanisms_x000D_ _x000D_ Methods_x000D_ Clinical studies_x000D_ Tumour material will be collected from high risk patients with AK/KSC, who will also be entered into relevant clinical trials of agents preventing and treating skin cancer. HPV genotyping and clinico-pathological data will be used to stratify patient groups for tumour stage and identified risk factors. We will continue to develop matched cSCC lines for in vitro studies and transplantation models. Participation into European and international studies of the role of HPV and molecular pathogenesis of cSCC will continue together with new research on immune mechanisms_x000D_ Molecular mechanisms _x000D_ Having identified specific genetic abnormalities in KSC, the future studies will focus on 3 main target areas. 1. PTPRD microdeletions in poor prognosis KSC; 2. Polo-1 kinase and c20orf20 as drivers of KSC growth; 3. Dysregulation of TGF beta pathway in KSC. Future functional studies will include manipulation of tumour keratinocytes in vitro and in a newly established xenotransplantation model of human skin carcinogenesis. High throughput screening will search for additional therapeutic targets particularly those which can be translated to the clinic in a short time frame._x000D_ _x000D_ How the results will be used_x000D_ This programme directly studies human skin cancer and can be rapidly translated into optimised diagnosis, prevention and treatment of skin cancer. A large number of national and international research collaborations will facilitate dissemination, application and exploitation.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS