title: Predictive molecular pathology and its role in targeted cancer therapy: a review focussing on clinical relevance.
abstract: The increasing importance of targeting drugs in the treatment of several tumor entities (breast, colon, lung, malignant melanoma (MM), lymphoma, and so on) and the necessity of a companion diagnostic (human epidermal growth factor receptor 2, Kirsten rat sarcoma viral oncogene, epidermal growth factor receptor (EGFR), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), and so on) is leading to new challenges for surgical pathology. As all the biomarkers to be specifically detected are tissue based, a precise and reliable diagnostic is absolutely crucial. To meet this challenge, surgical pathology has adapted a number of molecular methods (semi-quantitative immunohistochemistry, fluorescence in situ hybridization), PCR and its multiple variants, (pyro/Sanger) sequencing, next-generation sequencing, DNA-arrays, methylation analyses, and so on) to be applicable for formalin-fixed paraffin-embedded (FFPE) tissue. To read a patients' tissue as 'deeply' as possible and to obtain information on morphological, genetic, proteomic as well as epigenetic background is the actual task of pathologists and molecular biologists in order to provide the clinicians with information relevant for individualized medicine. The intensified cooperation of clinicians and pathologists will provide the basis of improved clinical drug selection as well as guide development of new cancer gene therapies and molecularly targeted drugs by research units and the pharmaceutical industry. This review will give some information on (1) biomarker detection methods adapted to FFPE tissue, (2) the potency of predictive pathology in tumor detection and treatment and (3) the implications of pathology on the development of new drugs in molecularly targeted and gene therapies.
authors.affiliation: Institute of Pathology, Charité, University Medicine Berlin, Berlin, Germany. manfred.dietel@charite.de
authors.forename: M
authors.initials: M
authors.lastname: Dietel
authors.forename: K
authors.initials: K
authors.lastname: Jöhrens
authors.forename: Mv
authors.initials: M
authors.lastname: Laffert
authors.forename: M
authors.initials: M
authors.lastname: Hummel
authors.forename: H
authors.initials: H
authors.lastname: Bläker
authors.forename: B M
authors.initials: BM
authors.lastname: Müller
authors.forename: A
authors.initials: A
authors.lastname: Lehmann
authors.forename: C
authors.initials: C
authors.lastname: Denkert
authors.forename: F L
authors.initials: FL
authors.lastname: Heppner
authors.forename: A
authors.initials: A
authors.lastname: Koch
authors.forename: C
authors.initials: C
authors.lastname: Sers
authors.forename: I
authors.initials: I
authors.lastname: Anagnostopoulos
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D025202:Molecular Diagnostic Techniques; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D057285:Precision Medicine
chemical_list: D014408:Biomarkers, Tumor