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Updated: Feb 21, 2026
A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing Neoadjuvant Therapies
Published on: July 28, 2020
Dermatofibrosarcoma protuberans and gastrointestinal stromal tumor as models for targeted therapy in soft tissue
Hanna Koseła-Paterczyk1, Piotr Rutkowski1
1a Department of Soft Tissue/Bone Sarcoma and Melanoma , Maria Sklodowska-Curie Institute Oncology Center , Warsaw , Poland.
Introduction:
The development of novel targeted treatment in soft tissue sarcomas (STS) is important since many sarcoma subtypes are resistant to chemotherapy and effective therapeutic options are limited. Areas covered: This review discusses the molecular background and treatment in two STS types which became a model for targeted therapy - gastrointestinal stromal tumor (GIST) and dermatofibrosarcoma protuberans (DFSP). DFSP is characterized, by chromosomal translocation which results in the formation of COL1A1-PDGFB fusion gene causing platelet-derived growth factor receptor beta(PDGFRB) signaling activation in tumor cells. The majority of GIST malignancies are associated with activating, constitutive, mutually exclusive mutations of two genes: KIT and PDGFRA (PDGF receptor-alpha). Molecular diagnostics are an essential part of GIST and DFSP management. The first effective systemic therapy in clinical practice in GIST and DFSP was imatinib - tyrosine kinase inhibitor acting on KIT and PDGFR alpha/beta. Use of the drug revolutionized treatment of inoperable and/or metastatic cases and demonstrated activity in locally advanced cases. This review summarizes the analogies of therapy and perspectives of GIST and DFSP management. Expert commentary: The next generation of kinase inhibitors are approved for use after the progression of GIST during imatinib treatment. However, little is known about treatment beyond progression in DFSP.
Insights
Targeted therapies like imatinib have revolutionized soft tissue sarcoma (STS) treatment, particularly for gastrointestinal stromal tumors (GIST) and dermatofibrosarcoma protuberans (DFSP). Further research is needed for DFSP treatment beyond progression.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Soft tissue sarcomas (STS) often resist chemotherapy, necessitating novel targeted treatments.
- Gastrointestinal stromal tumors (GIST) and dermatofibrosarcoma protuberans (DFSP) serve as models for targeted therapy development.
- DFSP involves COL1A1-PDGFB fusion and PDGFRB signaling; GIST involves KIT and PDGFRA mutations.
Purpose of the Study:
- To review the molecular basis and treatment strategies for GIST and DFSP.
- To highlight analogies in therapy and future perspectives for managing these STS subtypes.
- To discuss the role of molecular diagnostics and targeted therapies in STS treatment.
Main Methods:
- Literature review focusing on molecular mechanisms and therapeutic interventions in GIST and DFSP.
- Analysis of targeted therapies, including imatinib and next-generation kinase inhibitors.
- Examination of treatment outcomes and challenges in managing these specific STS.
Main Results:
- Imatinib, a tyrosine kinase inhibitor, demonstrated significant efficacy in GIST and DFSP, transforming treatment paradigms.
- Molecular diagnostics are crucial for effective GIST and DFSP management.
- Next-generation kinase inhibitors are available for GIST progression, but DFSP treatment beyond progression remains less understood.
Conclusions:
- Targeted therapies have greatly improved outcomes for GIST and DFSP.
- Understanding the molecular drivers is key to developing effective treatments for STS.
- Further investigation into treatment strategies for DFSP beyond progression is warranted.
