title: Improved insight into resistance mechanisms to imatinib in gastrointestinal stromal tumors: a basis for novel approaches and individualization of treatment.
abstract: Gastrointestinal stromal tumor (GIST) is one of the first solid tumor types in which a tyrosine kinase inhibitor, imatinib, has become standard of care for patients with advanced disease. Although imatinib yields antitumor activity in the vast majority of patients, it is likely that all patients eventually experience progressive disease given enough time. In recent years, major progress has been made in the elucidation of mechanisms conferring resistance to imatinib that result in progressive disease. Insight into these resistance mechanisms has already resulted in the availability of strategies that can be applied in cases of progressive disease and it is likely that more approaches will be defined in the next years. Additionally, it can be anticipated that in the near future treatment will be guided according to factors determining sensitivity to imatinib. This review focuses on the factors inducing imatinib resistance that have been elucidated so far, the currently available and potential novel treatment options for patients with progressive disease, and how insight into resistance mechanisms may allow individualized treatment in the near future for patients with advanced GISTs.
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Centre, Daniel den Hoed Cancer Centre, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands. s.sleijfer@erasmusmc.nl
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
authors.forename: Erik
authors.initials: E
authors.lastname: Wiemer
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.forename: Jaap
authors.initials: J
authors.lastname: Verweij
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001549:Benzamides; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007211:Indoles; D010879:Piperazines; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; D000077210:Sunitinib