{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["9(65)"],"submitter":["Sogaard CK"],"pubmed_abstract":["Low response rate and rapid development of resistance against commonly used chemotherapeutic regimes demand new multi-targeting anti-cancer strategies. In this study, we target the stress-related roles of the scaffold protein PCNA with a cell-penetrating peptide containing the PCNA-interacting motif APIM. The APIM-peptide increased the efficacy of cisplatin-based therapies in a muscle-invasive bladder cancer (MIBC) solid tumor model in rat and in bladder cancer (BC) cell lines. By combining multiple omics-levels, from gene expression to proteome/kinome and metabolome, we revealed a unique downregulation of the EGFR/ERBB2 and PI3K/Akt/mTOR pathways in the APIM-peptide-cisplatin combination treated cells. Additionally, the combination treatment reduced the expression of anti-apoptotic protei"],"journal":["Oncotarget"],"pagination":["32448-32465"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6126690"],"repository":["biostudies-literature"],"pubmed_title":["\"Two hits - one stone\"; increased efficacy of cisplatin-based therapies by targeting PCNA's role in both DNA repair and cellular signaling."],"pmcid":["PMC6126690"],"pubmed_authors":["Sogaard CK","Rost LM","Petrovic V","Nepal A","Otterlei M","Gederaas OA","Bachke S","Bruheim P","Blindheim A","Viset T","Arum CJ","Liabakk NB"],"additional_accession":[]},"is_claimable":false,"name":"\"Two hits - one stone\"; increased efficacy of cisplatin-based therapies by targeting PCNA's role in both DNA repair and cellular signaling.","description":"Low response rate and rapid development of resistance against commonly used chemotherapeutic regimes demand new multi-targeting anti-cancer strategies. In this study, we target the stress-related roles of the scaffold protein PCNA with a cell-penetrating peptide containing the PCNA-interacting motif APIM. The APIM-peptide increased the efficacy of cisplatin-based therapies in a muscle-invasive bladder cancer (MIBC) solid tumor model in rat and in bladder cancer (BC) cell lines. By combining multiple omics-levels, from gene expression to proteome/kinome and metabolome, we revealed a unique downregulation of the EGFR/ERBB2 and PI3K/Akt/mTOR pathways in the APIM-peptide-cisplatin combination treated cells. Additionally, the combination treatment reduced the expression of anti-apoptotic protei","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Aug","modification":"2026-04-13T19:17:00.048Z","creation":"2019-03-26T23:55:34Z"},"accession":"S-EPMC6126690","cross_references":{"pubmed":["30197755"],"doi":["10.18632/oncotarget.25963"]}}