title: Dermatofibrosarcoma protruberans treatment with platelet-derived growth factor receptor inhibitor:  a review of clinical trial results.
abstract: OBJECTIVE
  Dermatofibrosarcoma protuberans (DFSP) is a rare mesenchymal neoplasm arising in the dermis, accounting for less than 0.1% of all cancers. Given its rarity, and paucity of randomized trials, the nuances of treatment are not widely understood. In this review we attempt to summarize the available data to guide treatment choices for physicians managing this disease.
  
  
  RESULTS
  DFSP carries a translocation of chromosomes 17 and 22 leading to juxtaposition of the collagen type-1α1 promoter to the platelet-derived growth factor (PDGF) gene. This results in unregulated expression of PDGF leading to autocrine or paracrine activation of its receptor (PDGFRβ). This molecular pathway is the target of our current drug therapy for DFSP, imatinib, a tyrosine kinase inhibitor that interferes with the phosphorylation and activation of PDGFRβ. In case reports and prospective studies, imatinib was noted to be an effective treatment for patients with unresectable or metastatic DFSP, associated with response rates approaching 50%. It has also been used preoperatively to improve the resectability of tumors. Since metastasis is rarely seen and local recurrences are uncommon following wide excision with pathologically negative margins, surgery remains the backbone of treatment.
  
  
  CONCLUSIONS
  Imatinib, a tyrosine kinase inhibitor, is the current preferred agent for treatment of unresectable or metastatic DFSP. Clinical trials evaluating broader-spectrum kinase inhibitors such as pazopanib are in development.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA.
authors.forename: Binu
authors.initials: B
authors.lastname: Malhotra
authors.forename: Scott M
authors.initials: SM
authors.lastname: Schuetze
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D002986:Clinical Trials as Topic; D018223:Dermatofibrosarcoma / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D017479:Receptors, Platelet-Derived Growth Factor