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Updated: Mar 18, 2026
Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
Published on: April 11, 2018
Preclinical evaluation of potential therapeutic targets in dedifferentiated liposarcoma
Robert Hanes1,2, Iwona Grad1, Susanne Lorenz1,2
1Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Abstract:
Sarcomas are rare cancers with limited treatment options. Patients are generally treated by chemotherapy and/or radiotherapy in combination with surgery, and would benefit from new personalized approaches. In this study we demonstrate the potential of combining personal genomic characterization of patient tumors to identify targetable mutations with in vitro testing of specific drugs in patient-derived cell lines. We have analyzed three metastases from a patient with high-grade metastatic dedifferentiated liposarcoma (DDLPS) by exome and transcriptome sequencing as well as DNA copy number analysis. Genomic aberrations of several potentially targetable genes, including amplification of KITLG and FRS2, in addition to amplification of CDK4 and MDM2, characteristic of this disease, were identified. We evaluated the efficacy of drugs targeting these aberrations or the corresponding signaling pathways in a cell line derived from the patient. Interestingly, the pan-FGFR inhibitor NVP-BGJ398, which targets FGFR upstream of FRS2, strongly inhibited cell proliferation in vitro and induced an accumulation of cells into the G0 phase of the cell cycle. This study indicates that FGFR inhibitors have therapeutic potential in the treatment of DDLPS with amplified FRS2.
Insights
This study explored personalized medicine for dedifferentiated liposarcoma (DDLPS) by analyzing tumor mutations and testing targeted drugs. FGFR inhibitors showed promise for treating DDLPS with amplified FRS2.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- Sarcomas, including dedifferentiated liposarcoma (DDLPS), are rare cancers with limited therapeutic options.
- Current treatments involve surgery, chemotherapy, and radiotherapy, highlighting the need for personalized approaches.
- Identifying targetable mutations in patient tumors is crucial for developing novel therapies.
Purpose of the Study:
- To investigate the potential of combining genomic characterization of patient tumors with in vitro drug testing for personalized sarcoma treatment.
- To identify targetable genomic aberrations in a patient with high-grade metastatic dedifferentiated liposarcoma (DDLPS).
- To evaluate the efficacy of drugs targeting identified aberrations or their signaling pathways in a patient-derived cell line.
Main Methods:
- Exome sequencing, transcriptome sequencing, and DNA copy number analysis were performed on three metastases from a DDLPS patient.
- Genomic aberrations, including amplifications of KITLG, FRS2, CDK4, and MDM2, were identified.
- A patient-derived cell line was used to test the efficacy of drugs targeting identified aberrations and their pathways.
Main Results:
- Genomic analysis revealed characteristic amplifications of CDK4 and MDM2, along with amplifications of KITLG and FRS2.
- The pan-FGFR inhibitor NVP-BGJ398 demonstrated significant inhibition of cell proliferation in vitro.
- NVP-BGJ398 treatment led to cell cycle arrest in the G0 phase.
Conclusions:
- FGFR inhibitors, such as NVP-BGJ398, show therapeutic potential for treating dedifferentiated liposarcoma (DDLPS).
- Targeting FGFR, which is upstream of FRS2, is a viable strategy for DDLPS with amplified FRS2.
- This study supports the integration of personal genomic profiling and targeted drug screening for advancing sarcoma treatment.
