title: Beyond standard therapy: drugs under investigation for the treatment of gastrointestinal stromal tumor.
abstract: BACKGROUND
  Gastrointestinal stromal tumor (GIST) is the most common nonepithelial malignancy of the GI tract. With the discovery of KIT and later platelet-derived growth factor α (PDGFRA) gain-of-function mutations as factors in the pathogenesis of the disease, GIST was the quintessential model for targeted therapy. Despite the successful clinical use of imatinib mesylate, a selective receptor tyrosine kinase (RTK) inhibitor that targets KIT, PDGFRA and BCR-ABL, we still do not have treatment for the long-term control of advanced GIST.
  
  
  METHODS
  This review summarizes the drugs that are under investigation or have been assessed in trials for GIST treatment. The article focuses on their mechanisms of actions, the preclinical evidence of efficacy, and the clinical trials concerning safety and efficacy in humans.
  
  
  CONCLUSIONS
  It is known that KIT and PDGFRA mutations in GIST patients influence the response to treatment. This observation should be taken into consideration when investigating new drugs. RECIST was developed to help uniformly report efficacy trials in oncology. Despite the usefulness of this system, many questions are being addressed about its validity in evaluating the true efficacy of drugs knowing that new targeted therapies do not affect the tumor size as much as they halt progression and prolong survival.
authors.affiliation: University of Kansas Medical Center, Department of Pathology and Laboratory Medicine , Kansas City, Kansas , USA.
authors.forename: Hani J
authors.initials: HJ
authors.lastname: Alturkmani
authors.forename: Ziyan Y
authors.initials: ZY
authors.lastname: Pessetto
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Godwin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D015195:Drug Design; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational
keywords: gastrointestinal stromal tumor; imatinib mesylate; investigational drugs; repurposed drugs; targeted therapy; tyrosine kinase inhibitor