Systemic therapy for advanced gastrointestinal stromal tumors: beyond imatinib

J Surg Oncol. 2011 Dec;104(8):901-6. doi: 10.1002/jso.21872.

Abstract

Progression on first-line therapy with imatinib in gastrointestinal stromal tumors (GIST) is caused by either initial resistance or more often a secondary mutation in tyrosine kinases KIT or PDGFR. Therapies in development for imatinib-resistant GIST include agents that target KIT/PDGFR with greater potency or possess broader kinase inhibition profiles including VEGFR. To circumvent secondary mutations in KIT/PDGFR, inhibition of the downstream signaling in PI3K/Akt/mTOR pathway and enhanced degradation of KIT/PDGFR are also under investigation.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Gastrointestinal Neoplasms / drug therapy*
  • Gastrointestinal Neoplasms / genetics
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / genetics
  • Humans
  • Imatinib Mesylate
  • Indoles / therapeutic use
  • Mutation
  • Piperazines / therapeutic use*
  • Piperidines
  • Proto-Oncogene Proteins c-kit / genetics
  • Pyridines
  • Pyrimidines / therapeutic use*
  • Pyrroles / therapeutic use
  • Receptors, Platelet-Derived Growth Factor / genetics
  • Sunitinib
  • Thiazoles / therapeutic use

Substances

  • Antineoplastic Agents
  • Benzamides
  • Indoles
  • Piperazines
  • Piperidines
  • Pyridines
  • Pyrimidines
  • Pyrroles
  • Thiazoles
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit
  • Receptors, Platelet-Derived Growth Factor
  • nilotinib
  • masitinib
  • Sunitinib