Dermatofibrosarcoma protuberans and gastrointestinal stromal tumor as models for targeted therapy in soft tissue sarcomas.

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.