title: Why tyrosine kinase inhibitor resistance is common in advanced gastrointestinal stromal tumors.
abstract: BACKGROUND
  Most patients with advanced gastrointestinal stromal tumors (GIST) develop drug resistance to tyrosine kinase inhibitors (TKIs) within two years of starting therapy, whereas most chronic myeloid leukemia (CML) patients in chronic phase still exhibit disease control after a decade on therapy. This article aims to explain this divergence in long term outcomes.
  
  
  RESULTS
  By combining clinical and experimental observations with mathematical formulas we estimate that, in advanced GIST, the genetic changes responsible for resistance are generally already present at disease detection.
  
  
  CONCLUSIONS
  This result has relevant clinical implications by providing support for the exploration of combination therapies.
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston MA, 02215, USA ; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston MA, 02215, USA ; Current affiliation: Division of Biostatistics & Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD , 21205-2013 , USA ; Current affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205-2179 , USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Tomasetti
authors.affiliation: Ludwig Center for Cancer Research at Dana-Farber Cancer Institute and Harvard Medical School, Boston MA, 02215, USA ; Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston MA, 02215, USA.
authors.forename: George D
authors.initials: GD
authors.lastname: Demetri
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston MA, 02215, USA ; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston MA, 02215, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Parmigiani