Inhibition of KIT Tyrosine Kinase Activity: Two Decades after the First Approval.

Article Tools BIOLOGY OF NEOPLASIA Precision Oncology Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.20.03245 Journal of Clinical Oncology - published online before print April 2, 2021 PMID: 33797935 Inhibition of KIT Tyrosine Kinase Activity: Two Decades After the First Approval Lillian R. Klug, PhD1,2,3xLillian R. KlugSearch for articles by this author; Christopher L. Corless, MD, PhD1,4xChristopher L. CorlessSearch for articles by this author; and Michael C. Heinrich , MD1,2,3xMichael C. HeinrichSearch for articles by this author Show More 1Oregon Health & Science University, Knight Cancer Institute, Portland, OR2Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR3VA Portland Health Care System, Portland, OR4Department of Pathology, Oregon Health & Science University, Portland, OR https://doi.org/10.1200/JCO.20.03245 First Page Full Text PDF Figures and Tables © 2021 by American Society of Clinical OncologyCONTEXTKey ObjectiveImatinib, the first kinase inhibitor for cancer treatment, was developed over 20 years ago. In that time, imatinib as a KIT-targeted therapy revolutionized the treatment of patients with KIT-driven malignancies, primarily GI stromal tumor and systemic mastocytosis, and led to the development of additional KIT inhibitors that have significantly improved patient outcomes. We explore the history of KIT-targeted therapies beginning with imatinib.Knowledge GeneratedNumerous lessons have been learned from the initial preclinical and clinical studies with imatinib and other KIT inhibitors. The clinical use of imatinib has also provided the basis to understand the molecular properties of KIT and its interactions with drugs, allowing for rational design of more successful KIT inhibitors.RelevanceThe development of imatinib, as well as later-line KIT-targeted kinase inhibitors, has transformed the way we treat GI stromal tumors and mast cell malignancies. Further understanding of KIT biology and resistance mechanisms will further inform and refine our treatment of KIT-driven diseases.AUTHOR CONTRIBUTIONSConception and design: Michael C. HeinrichFinancial support: Michael C. HeinrichAdministrative support: Christopher L. Corless, Michael C. HeinrichCollection and assembly of data: Lillian R. Klug, Michael C. HeinrichData analysis and interpretation: Christopher L. CorlessManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTInhibition of KIT Tyrosine Kinase Activity: Two Decades After the First ApprovalThe following represents disclosure information provided by the authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Christopher L. CorlessEmployment: Omics Data AutomationLeadership: Omics Data AutomationStock and Other Ownership Interests: Guardant Health, Omics Data AutomationHonoraria: RocheConsulting or Advisory Role: Roche, Thermo Fisher Scientific Biomarkers, Cepheid, AmgenResearch Funding: Aileron Therapeutics, ArvinasTravel, Accommodations, Expenses: Roche, Thermo Fisher Scientific, CepheidOpen Payments Link: https://openpaymentsdata.cms.gov/physician/1233373Michael C. HeinrichStock and Other Ownership Interests: MolecularMDHonoraria: NovartisConsulting or Advisory Role: MolecularMD, Novartis, Blueprint Medicines, DecipheraPatents, Royalties, Other Intellectual Property: Patent on treatment of GIST-licensed to NovartisExpert Testimony: NovartisNo other potential conflicts of interest were reported.