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

Abstract

ABSTRACTIntroduction: 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.