Oncologist's/haematologist's view on the roles of pathologists for molecular targeted cancer therapy

Introduction Techniques used for diagnosis and monitoring of malignant diseases treated with targeted therapies Chronic myelogenous leukaemia: the poster child of targeted therapy Bcr-Abl as a target for therapeutic kinase inhibition Preclinical and clinical development of the TKI imatinib CML: molecular diagnostics guide treatment Lessons learned from CML targeted therapy: c-Kit, PDGFR and EGFR dependent tumours Treating cancer with EGFR targeting therapy EGFR mutations in non-small cell lung cancer: molecular characteristics outweigh clinical characteristics EGFR, EGFRvIII and other markers in head and neck cancer EGFR and KRAS, BRAF and PIK3CA mutations in colorectal cancer Diagnostic use of gene expression analysis: carcinoma of unknown primary Prognostic relevance of gene expression analysis: diffuse large B-cell lymphoma The role of biomarker analysis within clinical trials - involvement of pathologists Identification and validation of predictive biomarkers in trials evaluating molecular targeted treatments Assessment of optimal drug dose, schedule and treatment combinations Summary In the past two decades there has been a tremendous increase in the understanding of the molecular basis of human malignancies. In a variety of neoplasms, specific molecular markers became part of disease classifications and are now routinely used to define specific entities. Molecular analyses discriminate prognostic groups, guide differential treatment strategies and identify targets for molecular defined cancer therapy. A battery of new drugs has been developed to specifically inhibit oncogenic pathways. For an increasing number of solid and haematological malignancies, the availability of molecular targeted drugs has fundamentally changed treatment algorithms. However, the diagnostic, prognostic and therapeutic impact of selected molecular markers is still limited in many cases. After all, the success of a molecular targeted therapy is clearly determined by the significance of the targeted structure for the biology of cancer and the ability of the malignant cell to evade specific inhibition.