title: Theranostic proteomic profiling of cyclins, cyclin dependent kinases and Ras in human cancer cell lines is dependent on p53 mutational status.
abstract: Despite major advances in the molecular biology of the cancer cell over the past two decades, the great majority of patients are still treated by conventional cytotoxic drugs. The chemotherapy regimens employed frequently include platinating agents, taxanes, intercalating agents and topoisomerase inhibitors. Attempts to predict the therapeutic efficacy of such drugs by molecular profiling (theranostics) have up to the present time had limited success. Genes responsible for the control of cell division, senescence and apoptosis whose normal functions become corrupted during carcinogenesis, might potentially play a part in determining chemotherapeutic response. Here we have examined the relationships between the chemoresponsiveness of 18 human in vitro cancer cell lines and proteomic expression of Ras, cyclins B1 and D1 and cyclin-dependent kinases Cdk1 and Cdk4. When all 18 cell lines were examined as a single group, proteomic expression did not provide any helpful theranostic predictors. Clear relationships between proteomic expression and drug efficacy emerged, however, when Ras, cyclin B1, cyclin D1, Cdk1 and Cdk4 were examined separately in p53 wild-type and p53 mutant cell subsets. We suggest that the theranostic relationships we have detected in vitro may have potential relevance in vivo and should prompt clinical theranostic studies which take account of p53 mutational status.
authors: School of Chemistry, University of Southampton, Highfield, Southampton, UK. h.warenius@soton.ac.uk
authors: Hilmar M
authors: HM
authors: Warenius
authors: Laurence
authors: L
authors: Seabra
authors: Lito
authors: L
authors: Kyritsi
authors: Ros
authors: R
authors: White
authors: Roisin
authors: R
authors: Dormer
authors: Shanez
authors: S
authors: Anandappa
authors: Carole
authors: C
authors: Thomas
authors: Amanda
authors: A
authors: Howarth
mesh_terms: D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D018844:Cyclin-Dependent Kinases / Q000032:analysis*; D016213:Cyclins / Q000032:analysis*; D016158:Genes, p53; D006801:Humans; D016014:Linear Models; D009154:Mutation; D009369:Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics; D040901:Proteomics; D018631:ras Proteins / Q000032:analysis*
chemical_list: D016213:Cyclins; D018844:Cyclin-Dependent Kinases; D018631:ras Proteins; D002945:Cisplatin