Imatinib as effective therapy for dermatofibrosarcoma protuberans: proof of concept of the autocrine hypothesis for cancer.
Cancer literature has consistently described autocrine loops involving growth factors to be important mechanisms for cellular transformation and proliferation in preclinical cancer models. Finally, convincing clinical data exist to implicate autocrine loops as central to the pathogenesis of a malignant condition, largely as a result of the recent development of inhibitors of protein tyrosine kinases important in cell signaling and growth. Although a rare condition, the study of patients with dermatofibrosarcoma protuberans (DFSP) is enriched by data demonstrating strong scientific rationale for its pathogenesis and susceptibility to molecular-based therapies. DFSP is a low-grade sarcoma that responds to treatment with imatinib, an inhibitor of the PDGF receptor tyrosine kinase. This treatment response illustrates the importance of autocrine/paracrine loops involving PDGF and its receptor as the key molecular target in DFSP. New insight into this fundamental biological mechanism sets the scene for the further development of molecular-targeted therapeutic options for cancer.
Handolias
Despina
D
Peter MacCallum Cancer Centre, Department of Haematology and Medical Oncology, Locked Bag 1, A'Beckett Street, Victoria 8006, Australia.
McArthur
Grant A
GA
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019898:Autocrine Communication / Q000187:drug effects*; D001549:Benzamides; D018223:Dermatofibrosarcoma / Q000188:drug therapy* / Q000503:physiopathology*; D004815:Epidermal Growth Factor / Q000502:physiology; D066246:ErbB Receptors / Q000502:physiology; D006801:Humans; D000068877:Imatinib Mesylate; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D017526:Receptor, IGF Type 1 / Q000502:physiology; D017978:Receptors, Growth Factor / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D000970:Antineoplastic Agents; D001549:Benzamides; D036341:Intercellular Signaling Peptides and Proteins; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D011743:Pyrimidines; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D000068877:Imatinib Mesylate; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1; D040262:Receptors, Vascular Endothelial Growth Factor