Methodological Approaches towards Personalised Cancer Medicine

摘要: Despite advances in diagnostics and treatments, many cancer patients have poor survival rates. Tumours develop drug resistance followed by metastasis, survivors suffer from treatment side-effects. Omics techniques, targeted treatments immunotherapy offer the prospect of individually adapting for optimal efficacy minimal This requires integration biomolecular, clinical data to successfully predict every patient. The aim this thesis was evaluate apply different methodologies important personalised a variety settings. first paper showed that E6/E7 mRNA detection through RT-NASBA is more accurate sensitive than DNA genotyping classifying HPV infection cervical adenocarcinoma, showing RNA analysis be preferable identifying high-risk patients. In II, HPV16 E2 E5 expression oropharyngeal analysed relation outcomes tumour immunology. Neither down-regulation HLA class I nor CD8 + T-cell infiltration, both indicators good prognosis, were dependent on or E5. However, absence related progression-free survival. allows combined with T-cells when stratifying prognosis milder treatment. third screened combinations growth factors drugs impact proliferation breast cells, creating two-dimensional space simulate tumours signalling states interacting drugs. MDA-MB-231 TGF-β combination EGF oestrogen inhibited growth, effect strengthened Tamoxifen. MCF7 Tamoxifen added oestrogen. IV, immunoproteome urinary bladder analysed. Proteomics network regulatory (Treg) effector (Teff) lymph nodes Tregs sentinel (SN) up-regulate immune networks. IL16, previously not shown expressed Tregs, predicted as central SN-Treg signalling. IL-16 validated, higher peripheral blood cell supernatant. conclusion, has methods improve patient stratification adenocarcinoma HPV-positive cancer. utility screenings replicating heterogeneity optimising demonstrated, finally, node proteomics revealed individual differences signalling, immunotherapy. Integration these other will key arrive at medicine – application LIST OF SCIENTIFIC PAPERS I. Hovland S, Muller Skomedal H, Mints M, Bergstrom J, Wallin KL, Karlsen F, Johansson B, Andersson S. analysis: test objective assessment prognostic procedure. Int J Oncol. 2010 Jun;36(6):1533-9. II. Ramqvist T * , M Tertipis N, Nasman A, Romanitan М, MunckWikland В, Dalianis T. Studies Human Papillomavirus (HPV) 16 E2, E7 Tonsillar Base Tongue Cancer Relation Clinical Outcome Immunological Parameters. Oral Oncology (In press). III. Souchelnytskyi Impact EGF, TGFβ, 17βoestradiol, inhibitors corresponding pathways lines. Exp 2014 Jun;36(2):67-71. IV. Krantz D, Winerdal Rutishauser Zubarev R, Zirakzadeh АA, Hansson Sherif Winqvist О. Individual subsets muscle-invasive urothelial reveals player tumour-Treg cross-talk. (Manuscript). *Shared authorship CONTENTS