title: Personalized Medicine in Gastrointestinal Stromal Tumor (GIST): Clinical Implications of the Somatic and Germline DNA Analysis.
abstract: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. They are characterized by gain of function mutations in KIT or PDGFRA tyrosine kinase receptors, with their consequent constitutive activation. The gold standard therapy is imatinib that offers a good and stable response for approximately 18-36 months. However, resistance is very common and it is vital to identify new biomarkers. Up until now, there have been two main approaches with focus to characterize novel targets. On the one hand, the focus is on the tumor genome, as the final clinical outcome depends mainly from the cancer specific mutations/alterations patterns. However, the germline DNA is important as well, and it is inconceivable to think the patients response to the drug is not related to it. Therefore the aim of this review is to outline the state of the art of the personalized medicine in GIST taking into account both the tumor DNA (somatic) and the patient DNA (germline).
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, via Irnerio 48, 40126 Bologna, Italy. gloria.ravegnini2@unibo.it.
authors.forename: Gloria
authors.initials: G
authors.lastname: Ravegnini
authors.affiliation: Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, 40138 Bologna, Italy. margherita.nannini@unibo.it.
authors.forename: Margherita
authors.initials: M
authors.lastname: Nannini
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, via Irnerio 48, 40126 Bologna, Italy. giulia.sammarini@studio.unibo.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Sammarini
authors.affiliation: "Giorgio Prodi" Cancer Research Center, University of Bologna, via Massarenti 11, 40126 Bologna, Italy. annalisa.astolfi@unibo.it.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Astolfi
authors.affiliation: Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, 40138 Bologna, Italy. guido.biasco@unibo.it.|"Giorgio Prodi" Cancer Research Center, University of Bologna, via Massarenti 11, 40126 Bologna, Italy. guido.biasco@unibo.it.
authors.forename: Guido
authors.initials: G
authors.lastname: Biasco
authors.affiliation: Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, 40138 Bologna, Italy. maria.pantaleo@unibo.it.|"Giorgio Prodi" Cancer Research Center, University of Bologna, via Massarenti 11, 40126 Bologna, Italy. maria.pantaleo@unibo.it.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pantaleo
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, via Irnerio 48, 40126 Bologna, Italy. patrizia.hrelia@unibo.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Hrelia
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, via Irnerio 48, 40126 Bologna, Italy. s.angelini@unibo.it.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Angelini
mesh_terms: D004273:DNA, Neoplasm / Q000032:analysis; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: GIST; KIT/PDGFRA mutant GIST; WT-GIST; biomarkers; drug resistance; personalized therapy; polymorphisms