Related Experiment Video
Updated: Sep 1, 2025
Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
Systemic Therapy for Gastrointestinal Stromal Tumor: Current Standards and Emerging Challenges
Wen-Kuan Huang1,2, Chiao-En Wu1,2, Shang-Yu Wang2,3
1Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
Opinion Statement:
Gastrointestinal stromal tumor (GIST), though rare, is the most common mesenchymal tumors of the gastrointestinal tract. KIT or PDGFRα mutation plays as an oncogenic driver in the majority of GISTs. Surgical resection is the only curative treatment for localized disease. The discovery of imatinib with promising anti-tumor effect and successive tyrosine kinase inhibitors (TKI), including second-line sunitinib and third-line regorafenib, revolutionized the management of advanced and metastatic GIST over the past two decades. Recently, ripretinib and avapritinib were approved for the fourth line setting and for PDGFRA exon 18-mutant GIST in first-line setting, respectively. Despite multi-line TKIs exerted ability of disease control, drug resistance remained an obstacle for preventing rapid disease progression. Experimental TKIs or novel therapeutic targets may further improve treatment efficacy. Immune checkpoint inhibitors such as anti-programmed cell death protein-1 (PD1) and anti-CTL-associated antigen 4 (CTLA-4) showed moderate response in early phase trials composed of heavily pretreated patients. KIT/PDGFRα wild-type GISTs are generally less sensitive to imatinib and late-line TKIs. Recent studies demonstrated that targeting fibroblast growth factor receptor signaling may be a potential target for the wild-type GISTs.
Insights
Gastrointestinal stromal tumors (GIST) are rare but common mesenchymal tumors. While tyrosine kinase inhibitors (TKIs) have advanced treatment, drug resistance and challenges in wild-type GISTs necessitate exploring novel therapies like FGFR inhibitors.
Area of Science:
- Oncology
- Gastrointestinal Pathology
- Molecular Targeted Therapy
Background:
- Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumors of the GI tract, often driven by KIT or PDGFRα mutations.
- Surgical resection offers curative potential for localized GIST.
- The advent of tyrosine kinase inhibitors (TKIs) like imatinib, sunitinib, and regorafenib has transformed the management of advanced and metastatic GIST.
Purpose of the Study:
- To review the current landscape of GIST treatment, including established and emerging therapies.
- To highlight the challenges posed by drug resistance and the management of KIT/PDGFRα wild-type GIST.
- To explore potential novel therapeutic targets for improving GIST treatment efficacy.
Main Methods:
- Review of clinical trial data and published literature on GIST management.
- Analysis of the efficacy and limitations of current multi-line TKI therapies.
- Exploration of emerging therapeutic strategies, including immune checkpoint inhibitors and targeting specific signaling pathways.
Main Results:
- Recent approvals of ripretinib and avapritinib expand fourth-line and first-line treatment options, respectively.
- Drug resistance remains a significant obstacle in advanced GIST, limiting long-term disease control.
- KIT/PDGFRα wild-type GISTs exhibit reduced sensitivity to standard TKIs, indicating a need for alternative approaches.
- Early trials suggest moderate responses with immune checkpoint inhibitors in heavily pretreated patients.
- Targeting fibroblast growth factor receptor (FGFR) signaling shows promise for wild-type GIST.
Conclusions:
- Despite advances with TKIs, overcoming drug resistance and treating wild-type GIST remain critical challenges.
- Novel therapeutic targets, including FGFR signaling, represent promising avenues for improving outcomes in GIST.
- Continued research into experimental TKIs and combination therapies is essential for advancing GIST management.
Related Concept Videos
01:21Inflammatory Bowel Disease V: Surgical Management
Here are some common surgical interventions for IBD:
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:56Treatment Resistant Cancers
01:15Drugs that Stabilize Microtubules
01:29Inflammatory Bowel Disease IV: Pharmacological Management
Pharmacologic...