title: Tissue-specific tumorigenesis: context matters.
abstract: How can we treat cancer more effectively? Traditionally, tumours from the same anatomical site are treated as one tumour entity. This concept has been challenged by recent breakthroughs in cancer genomics and translational research that have enabled molecular tumour profiling. The identification and validation of cancer drivers that are shared between different tumour types, spurred the new paradigm to target driver pathways across anatomical sites by off-label drug use, or within so-called basket or umbrella trials which are designed to test whether molecular alterations in one tumour entity can be extrapolated to all others. However, recent clinical and preclinical studies suggest that there are tissue- and cell type-specific differences in tumorigenesis and the organization of oncogenic signalling pathways. In this Opinion article, we focus on the molecular, cellular, systemic and environmental determinants of organ-specific tumorigenesis and the mechanisms of context-specific oncogenic signalling outputs. Investigation, recognition and in-depth biological understanding of these differences will be vital for the design of next-generation clinical trials and the implementation of molecularly guided cancer therapies in the future.
authors.affiliation: Department of Medicine II (Gastroenterology and GI Oncology), Klinikum rechts der Isar, Technische Universität München, School of Medicine, Ismaningerstr. 22, 81675 München, Germany; and at the German Cancer Research Center (DKFZ) and the German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Schneider
authors.affiliation: Department of Medicine III (Haematology and Oncology), Klinikum rechts der Isar, Technische Universität München, School of Medicine, Ismaningerstr. 22, 81675 München, Germany; and at the DKFZ and the DKTK, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Schmidt-Supprian
authors.affiliation: Department of Medicine II (Gastroenterology and GI Oncology), Klinikum rechts der Isar, Technische Universität München, School of Medicine, Ismaningerstr. 22, 81675 München, Germany; and at the German Cancer Research Center (DKFZ) and the German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Rad
authors.affiliation: University Hospital Klinikum rechts der Isar, Technische Universität München, School of Medicine, Ismaningerstr. 22, 81675 München, Germany; and at the Division of Translational Cancer Research, DKFZ and DKTK, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Saur
mesh_terms: D063646:Carcinogenesis; D054338:Cell Transdifferentiation; D002471:Cell Transformation, Neoplastic; D004249:DNA Damage; D004843:Epistasis, Genetic; D006801:Humans; D064307:Microbiota; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)