Differences in Signaling Patterns on PI3K Inhibition Reveal Context Specificity in
| Autor: | Adam, Stewart, Elizabeth A, Coker, Sebastian, Pölsterl, Alexandros, Georgiou, Anna R, Minchom, Suzanne, Carreira, David, Cunningham, Mary Er, O'Brien, Florence I, Raynaud, Johann S, de Bono, Bissan, Al-Lazikani, Udai, Banerji |
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| Rok vydání: | 2018 |
| Předmět: |
Proteomics
Proteome Gene Expression Profiling Antineoplastic Agents Phosphoproteins digestive system diseases Article respiratory tract diseases Gene Expression Regulation Neoplastic Proto-Oncogene Proteins p21(ras) Phosphatidylinositol 3-Kinases Cell Line Tumor Neoplasms Mutation Animals Humans neoplasms Protein Kinase Inhibitors Phosphoinositide-3 Kinase Inhibitors Signal Transduction |
| Zdroj: | Molecular cancer therapeutics. 18(8) |
| ISSN: | 1538-8514 |
| Popis: | It is increasingly appreciated that drug response to different cancers driven by the same oncogene is different and may relate to differences in re-wiring of signal transduction. We aimed to study differences in dynamic signaling changes within mutant KRAS (KRAS(MT)), non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and pancreatic adenocarcinoma (PDAC) cells. We used an antibody-based phosphoproteomic platform to study changes in 50 phosphoproteins caused by seven targeted anticancer drugs in a panel of 30 KRAS(MT) cell lines and cancer cells isolated from 10 patients with KRAS(MT) cancers. We report for the first time significant differences in dynamic signaling between CRC and NSCLC cell lines exposed to clinically relevant equimolar concentrations of the pan-PI3K inhibitor pictilisib including a lack of reduction of p-AKTser473 in CRC cell lines (P = 0.037) and lack of compensatory increase in p-MEK in NSCLC cell lines (P = 0.036). Differences in re-wiring of signal transduction between tumor types driven by KRAS(MT) cancers exist and influence response to combination therapy using targeted agents. |
| Databáze: | OpenAIRE |
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