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Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
Predictors of response to targeted therapies for gastrointestinal stromal tumors
Andrea Marrari1, Andrew J Wagner, Jason L Hornick
1Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Context:
The inhibition of oncogenic kinase signaling is a successful strategy to treat both hematologic and solid malignancies. Patients with chronic myelogenous leukemia, lung adenocarcinoma, renal cell carcinoma, and gastrointestinal stromal tumors are experiencing tremendous clinical benefits from targeted therapies in the form of kinase inhibitors. These drugs marked a revolution in cancer treatment, not only for their safety and efficacy, but also because they continue to expand our knowledge of the pathophysiology of cancer.
Objective:
To provide a summary of the biologic predictors of gastrointestinal stromal tumor behavior and response to targeted therapies that currently help guide clinical decision making.
Data Sources:
Published articles pertaining to the diagnosis, molecular genetics, prognostication, clinical behavior, and treatment of gastrointestinal stromal tumors, as well as experiences in a multidisciplinary sarcoma clinic.
Conclusions:
In gastrointestinal stromal tumors, the strongest predictor of response to targeted therapies is the mutational status of KIT or PDGFRA. Patients whose tumors harbor a KIT exon 11 mutation benefit the most from imatinib mesylate therapy, in terms of response rate, progression-free survival, and overall survival. Conversely, tumors without detectable mutations in either gene ("wild-type" gastrointestinal stromal tumors) are generally not responsive to imatinib mesylate.
Insights
The strongest predictor of gastrointestinal stromal tumor (GIST) response to targeted therapy is KIT or PDGFRA gene mutation status. KIT exon 11 mutations significantly improve outcomes with imatinib mesylate treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Targeted therapies, particularly kinase inhibitors, have revolutionized cancer treatment for various malignancies.
- These therapies offer significant clinical benefits and advance our understanding of cancer pathophysiology.
Purpose of the Study:
- To summarize biologic predictors of gastrointestinal stromal tumor (GIST) behavior.
- To outline predictors of GIST response to targeted therapies for clinical decision-making.
Main Methods:
- Review of published literature on GIST diagnosis, molecular genetics, prognostication, and treatment.
- Inclusion of experiences from a multidisciplinary sarcoma clinic.
Main Results:
- KIT or PDGFRA mutational status is the strongest predictor of GIST response to targeted therapies.
- Patients with KIT exon 11 mutations show the greatest benefit from imatinib mesylate.
Conclusions:
- Gastrointestinal stromal tumor (GIST) treatment response is strongly linked to specific gene mutations.
- Imatinib mesylate is most effective in GISTs with KIT exon 11 mutations; wild-type tumors generally do not respond.
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