Secondary KIT mutations: the GIST of drug resistance and sensitivity

2019/02/22 by Andrea Napolitano, Bruno Vincenzi · 27 citations
Medicine · #Gastrointestinal Tumor Research and Treatment #Gastric Cancer Management and Outcomes #Gastrointestinal disorders and treatments

paper · pdf · doi:10.1038/s41416-019-0388-7

Abstract

Pharmacological targeting of KIT in gastrointestinal stromal tumours has dramatically changed the clinical outcome of this disease. Tyrosine kinase inhibitors are the cornerstone of this improvement, but resistance occurs through secondary KIT mutations. Studies aimed at improving our understanding of the molecular basis of sensitivity and resistance will soon allow us to further tailor our therapeutic strategies.

Cited by

• Pimitespib: First Approval
• KIT Exon 9-Mutated Gastrointestinal Stromal Tumours: Biology and Treatment
• Review of precision cancer medicine: Evolution of the treatment paradigm. [europepmc]
• Targeted Deep Sequencing Uncovers Cryptic KIT Mutations in KIT/PDGFRA/SDH/RAS-P Wild-Type GIST. [europepmc]
• RAS/MAPK Pathway Driver Alterations Are Significantly Associated With Oncogenic KIT Mutations in Germ-cell Tumors. [europepmc]
• Sarcoma treatment in the era of molecular medicine. [europepmc]
• Therapeutic Potential of PI3K/AKT/mTOR Pathway in Gastrointestinal Stromal Tumors: Rationale and Progress. [europepmc]
• Early and Next-Generation KIT/PDGFRA Kinase Inhibitors and the Future of Treatment for Advanced Gastrointestinal Stromal Tumor. [europepmc]
• BRD9 inhibition promotes PUMA-dependent apoptosis and augments the effect of imatinib in gastrointestinal stromal tumors. [europepmc]
• EphA2 Expression in Bone Sarcomas: Bioinformatic Analyses and Preclinical Characterization in Patient-Derived Models of Osteosarcoma, Ewing's Sarcoma and Chondrosarcoma. [europepmc]
• FGFR2::TACC2 fusion as a novel KIT-independent mechanism of targeted therapy failure in a multidrug-resistant gastrointestinal stromal tumor. [europepmc]
• The Management of Unresectable, Advanced Gastrointestinal Stromal Tumours. [europepmc]
• Locoregional Treatments for Metastatic Gastrointestinal Stromal Tumor in British Columbia: A Retrospective Cohort Study from January 2008 to December 2017. [europepmc]
• Efficacy of SCF drug conjugate targeting c-KIT in gastrointestinal stromal tumor. [europepmc]
• FDA Approval Summary: Ripretinib for Advanced Gastrointestinal Stromal Tumor. [europepmc]
• The Prognostic Value of Plasma Programmed Death Protein-1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) in Patients with Gastrointestinal Stromal Tumor. [europepmc]
• Identification of Thiazolo[5,4- b ]pyridine Derivatives as c-KIT Inhibitors for Overcoming Imatinib Resistance. [europepmc]
• Emerging Data on the Safety and Efficacy of Ripretinib for the Treatment of Gastrointestinal Stromal Tumors. [europepmc]
• Molecular basis and therapeutic targets in prostate cancer: A comprehensive review. [europepmc]
• Molecular Tailored Therapeutic Options for Advanced Gastrointestinal Stromal Tumors (GISTs): Current Practice and Future Perspectives. [europepmc]
• Efficacy and safety of ripretinib in Chinese patients with advanced gastrointestinal stromal tumors: a real-world, multicenter, observational study. [europepmc]
• Cytoreductive surgery offers prognostic benefits in metastatic gastrointestinal stromal tumors with generalized progression following imatinib therapy: a single institute retrospective study. [europepmc]
• Clinicopathological, immunohistochemical, molecular-genetic and risk profiles of gastrointestinal stromal tumors in a cohort of Sudanese patients. [europepmc]
• Therapeutic advances of targeting receptor tyrosine kinases in cancer. [europepmc]
• Different efficacy of tyrosine kinase inhibitors by KIT and PGFRA mutations identified in circulating tumor DNA for the treatment of refractory gastrointestinal stromal tumors. [europepmc]
• Clinical impact of primary and secondary KIT mutations on the efficacy of molecular-targeted therapies in gastrointestinal stromal tumors. [europepmc]
• Targeting tumor dormancy: the next frontier in gastrointestinal stromal tumor therapy. [europepmc]

Related

• KIT Exon 9-Mutated Gastrointestinal Stromal Tumours: Biology and Treatment
• Mechanisms of Resistance to KRAS Inhibitors: Cancer Cells' Strategic Use of Normal Cellular Mechanisms to Adapt
• Co expression of SCF and KIT in gastrointestinal stromal tumours (GISTs) suggests an autocrine/paracrine mechanism
• Protein Kinase C θ (PKCθ) Expression and Constitutive Activation in Gastrointestinal Stromal Tumors (GISTs)
• N822K- or V560G-mutated KIT activation preferentially occurs in lipid rafts of the Golgi apparatus in leukemia cells