title: Therapeutic targeting of platelet-derived growth factor receptors in solid tumors.
abstract: BACKGROUND
  Genetic aberrations that are associated with platelet-derived growth factor receptor (PDGFR) activity are frequently found in glioblastomas (10 - 15%), dermatofibrosarcoma protuberans (≤ 100%) and gastrointestinal stromal tumors (5%). Sequencing studies have also identified mutations at lower frequency in common cancer types. Preclinical evidence further suggests tumor stimulatory roles of PDGFRs expressed by tumor stroma cells and indicates a deleterious effect of stromal PDGFRs on intratumoral drug uptake.
  
  
  METHODS
  This review summarizes the present understanding of PDGF signaling in solid tumors based on experimental studies and clinical findings. It also provides a discussion of selected ongoing efforts to develop novel cancer therapies involving PDGFR inhibition with tyrosine kinase inhibitors or PDGFR-targeting monoclonal antibodies.
  
  
  CONCLUSIONS
  An increased molecular understanding of response and resistance mechanisms will be essential for therapeutic advances in PDGFR-directed cancer therapy. Further developments rely on clinical studies where systematic analyses of target status in malignant cells and in cells of the tumor stroma are included. Studies with combination therapies will be facilitated by selective PDGFR inhibitors with reduced side effects. Finally, development of improved companion diagnostics is of critical importance for patient selection and monitoring of therapeutic effects.
authors.affiliation: Karolinska Institutet, Department of Oncology-Pathology , SE-17177 Stockholm , Sweden.
authors.forename: Monika
authors.initials: M
authors.lastname: Ehnman
authors.forename: Arne
authors.initials: A
authors.lastname: Östman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor