ReviewFrontiers in oncology2021
Early and Next-Generation KIT/PDGFRA Kinase Inhibitors and the Future of Treatment for Advanced Gastrointestinal Stromal Tumor.
Review in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 79 citations in OpenAlex.
- Precision therapeutic strategies for advanced gastrointestinal stromal tumors.Cancer metastasis reviews · 2026Review
- Rare Molecular Variants of Gastrointestinal Stromal Tumors (GISTs): Clinical Implications and Overview of Current Evidence.Targeted oncology · 2026Review
- Disproportionality analysis of adverse events associated with tyrosine kinase inhibitors in gastrointestinal stromal tumors in the FDA adverse event reporting system.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Patient and Tumor Factors Influencing Diagnostic Trajectories in Gastrointestinal Stromal Tumor Patients and Their Impact on Health-Related Quality of Life: A Dutch Multicenter Study.Annals of surgical oncology · 2026Observational
- Combinatorial Targeting of Avapritinib-Driven MAP Kinase Activation in High-Grade Glioma.Research square · 2026Article
- Different contributions of YAP1 and TAZ in the regulation of GIST tumorigenic properties.Cell communication and signaling : CCS · 2026Article
- [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Observational
- KIT Mutation-NTRK fusion oncogenic driver switch: a novel mechanism of acquired imatinib resistance in GIST.NPJ precision oncology · 2026Article
- Integrative genomic and immune landscape analysis of intimal sarcomas for emerging therapeutic targets and immunotherapy strategies.Frontiers in immunology · 2026Article
- Advancements in Drug Discovery Techniques for Cancer Treatment: Clinical Progress and Future Directions.Current drug discovery technologies · 2026Review
- The Evolving Role of Second- and Third-Generation Tyrosine Kinase Inhibitors in Gastrointestinal Malignancies: Advances in Targeted Therapy with Sunitinib, Regorafenib, and Avapritinib.Journal of clinical medicine · 2026Review
- Real-world regorafenib use among patients with advanced gastrointestinal stromal tumor in the United States.PloS one · 2026Article
- Molecular Mechanisms and Clinical Implications ofCurrent issues in molecular biology · 2025Review
- Identification of Molecular Subtypes of B-Cell Acute Lymphoblastic Leukemia in Mexican Children by Whole-Transcriptome Analysis.International journal of molecular sciences · 2025Article
- Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor After Imatinib Resistance.Pharmaceutics · 2025Review
- Effects of first‑line therapies in patients with locally advanced gastrointestinal stromal tumors withOncology letters · 2025Article
- Characteristics and therapeutic strategies for familial gastrointestinal stromal tumors.World journal of gastrointestinal oncology · 2025Article
- Discovery of novel PDGFR inhibitors targeting non-small cell lung cancer using a multistep machine learning assisted hybrid virtual screening approach.RSC advances · 2025Article
- Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects.Journal of biomedical science · 2025Review
- Intracranial germ cell tumors: advancement in genomic diagnostics and the need for novel therapeutics.Frontiers in oncology · 2025Review
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The majority of gastrointestinal stromal tumors (GIST) harbor an activating mutation in either the KIT or PDGFRA receptor tyrosine kinases. Approval of imatinib, a KIT/PDGFRA tyrosine kinase inhibitor (TKI), meaningfully improved the treatment of advanced GIST. Other TKIs subsequently gained approval: sunitinib as a second-line therapy and regorafenib as a third-line therapy. However, resistance to each agent occurs in almost all patients over time, typically due to secondary kinase mutations. A major limitation of these 3 approved therapies is that they target the inactive conformation of KIT/PDGFRA; thus, their efficacy is blunted against secondary mutations in the kinase activation loop. Neither sunitinib nor regorafenib inhibit the full spectrum of KIT resistance mutations, and resistance is further complicated by extensive clonal heterogeneity, even within single patients. To combat these limitations, next-generation TKIs were developed and clinically tested, leading to 2 new USA FDA drug approvals in 2020. Ripretinib, a broad-spectrum KIT/PDGFRA inhibitor, was recently approved for the treatment of adult patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib. Avapritinib, a type I kinase inhibitor that targets active conformation, was approved for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. In this review, we will discuss how resistance mutations have driven the need for newer treatment options for GIST and compare the original GIST TKIs with the next-generation KIT/PDGFRA kinase inhibitors, ripretinib and avapritinib, with a focus on their mechanisms of action.
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