title: Targeting protein kinase C in sarcoma.
abstract: Protein kinase C (PKC) is a family of serine/threonine tyrosine kinases that regulate many cellular processes including division, proliferation, survival, anoikis and polarity. PKC is abundant in many human cancers and aberrant PKC signalling has been demonstrated in cancer models. On this basis, PKC has become an attractive target for small molecule inhibition within oncology drug development programmes. Sarcoma is a heterogeneous group of mesenchymal malignancies. Due to their relative insensitivity to conventional chemotherapies and the increasing recognition of the driving molecular events of sarcomagenesis, sarcoma provides an excellent platform to test novel therapeutics. In this review we provide a structure-function overview of the PKC family, the rationale for targeting these kinases in sarcoma and the state of play with regard to PKC inhibition in the clinic.
authors.affiliation: Sarcoma Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.
authors.forename: J
authors.initials: J
authors.lastname: Martin-Liberal
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Cameron
authors.affiliation: Protein Phosphorylation Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: J
authors.initials: J
authors.lastname: Claus
authors.affiliation: Sarcoma Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.
authors.forename: I R
authors.initials: IR
authors.lastname: Judson
authors.affiliation: Protein Phosphorylation Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3LY, UK; Division of Cancer Studies, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Parker
authors.affiliation: Department of Oncology, University College London Cancer Institute, London, UK. Electronic address: mark.linch@uclh.nhs.uk.
authors.forename: M
authors.initials: M
authors.lastname: Linch
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D012509:Sarcoma / Q000188:drug therapy* / Q000201:enzymology; D015398:Signal Transduction
chemical_list: D011493:Protein Kinase C
keywords: Kinases; Protein kinase C; Sarcoma; Therapeutics