PDGF receptors as targets in tumor treatment.
Signaling through platelet-derived growth factor (PDGF) receptors contributes to multiple tumor-associated processes. The recent introduction of clinically useful PDGF inhibitors have the last years validated PDGF receptors in malignant and stromal cells as relevant cancer drug targets. Mutational activation of PDGF receptor signaling in malignant cells has been described in some rare tumor types such as dermatofibrosarcoma protuberans, a subset of GISTs, and some hematologic malignancies. Furthermore, expression of PDGF receptors on pericytes is a common characteristic of solid tumors. The clinical efficacy of novel multikinase inhibitors, such as sunitinib and sorafenib, most likely involves targeting of PDGF receptor-dependent pericytes. Preclinical studies suggest that targeting of stromal PDGF receptors might also constitute a novel strategy to enhance tumor drug uptake. Finally, recent studies have implied both pro- and antimetastatic effects of PDGF receptors on malignant and stromal cells. The studies on the roles of PDGF receptors in cancer signaling are thus presently in a dynamic phase where collaborations between oncologists, pathologists, and tumor biologists are predicted to be highly productive.
Ostman
Arne
A
Department of Pathology-Oncology, Cancer Center Karolinska, Karolinska Institutet, R8:03, SE-171 76 Stockholm, Sweden.
Heldin
Carl-Henrik
CH
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001549:Benzamides; D017326:Clinical Trials, Phase III as Topic; D016503:Drug Delivery Systems; D045604:Extracellular Fluid / Q000502:physiology; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D009154:Mutation; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000503:physiopathology; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011312:Pressure; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000077210:Sunitinib; D014178:Translocation, Genetic
D000970:Antineoplastic Agents; D001549:Benzamides; D007211:Indoles; D009363:Neoplasm Proteins; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; D017479:Receptors, Platelet-Derived Growth Factor; D000077210:Sunitinib