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P. Alberts
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-053 - Patient-Derived Xenograft Studies Suggest FGFR1 Amplification Is Insufficient to Predict Response to FGFR Inhibitors in Lung SqCC (ID 3067)
09:30 - 09:30 | Author(s): P. Alberts
- Abstract
Background:
FGFR1 amplification has been reported in 16%-20% of lung squamous cell carcinoma (SqCC). Early phase clinical trials with anti-FGFR small molecule inhibitors are in progress. It remains unclear whether genomic changes involving FGFR1 is associated with a dependency in FGFR-driven oncogenic activity that could be inhibited with pharmacologic agents. We evaluated a pan-FGFR inhibitor (BGJ398) in four SqCC patient-derived xenograft (PDX) models with amplification of the FGFR1 gene.
Methods:
FGFR1 gene copy changes were assessed by fluorescence in-situ hybridization. PDX models were established by implanting surgical resected tumor fragments into the subcutaneous tissue of non-obese diabetic severe combined immune deficient (NOD-SCID) mice. Protein and mRNA expression levels were assessed by immunohistochemistry/western blot and RT-qPCR, respectively.
Results:
FGFR1 amplification was observed in 13 of 60 (22%) SqCC patient tumors, with all amplified tumors forming PDX. PDX models with FGFR1 gene amplification displayed higher levels of mRNA and protein compared to non-amplified tumor, excluding polysomy cases. One model demonstrated an average of 50% decrease in tumor volume in the BGJ398 treated group compared to control group, 21 days post-treatment. This model also expressed high FGFR1 and high cMYC protein. BGJ398-resistant PDX models included one model with high FGFR1 but low cMYC protein levels, and two models with low FGFR1 and high cMYC protein levels.
Conclusion:
The lack of growth arrest to a pan-FGFR small molecule inhibitor in the 4 PDX models evaluated suggests that FGFR1 amplification alone was not a sufficient predictive marker for pan-FGFR1 inhibitor activity. FGFR1 protein and MYC protein are putative markers.
