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- W2039441350 abstract "Oncogenic events involve activation of kinases either in case of direct mutation or as a secondary event as recipients and mediators of oncogenic signals. Kinases transduce signals that lead to cell proliferation or inhibition of programmed cell death by activating transcription factors and inhibiting pro apoptotic molecules. Despite the knowledge and huge market for the kinases as targets, small molecule modulators have failed repeatedly to deliver as cancer therapeutics. Primarily, the failure is thought to stem from the lack of kinase discovery platforms that enable a mechanistic understanding of signaling pathways involving transmembrane and cytoplasmic kinases. The Berg Interrogative Biology® Kinase Discovery Platform offers novel technology driven solutions for understanding of kinases in oncogenesis. The approach is powered by “two-dimensional chemical interrogation” where in vitro cancer and control models were interrogated by a kinase inhibitor (sorafenib) in the first dimension. Overall changes in kinase activity were captured by a second dimension of chemical interrogation employing activity-based kinase enrichment probes. Kinases were identified by LC-MS based mass spectrometry. In addition, changes in phospho proteome in response to kinase inhibitor were captured using a phosphoprotein enrichment method followed by LC-MS for identification of proteins. Finally quantitative changes in total protein expression were obtained. Multi-omics data collated from the above mentioned approach was integrated using an AI-based informatics tool leading to generation of data-driven inference of causal networks representing differential kinase activity driving phosphorylation of proteins that are operational in cancer and not in normal models. The technology platform led to discovery of novel kinases that are mechanistically relevant to pathophysiology of cancer. Citation Format: Vivek K. Vishnudas, Min Du, Viatscheslav Akmaev, Rangaprasad Sarangarajan, Niven R. Narain. Two dimensional chemical interrogation of oncogenic systems and multi-omics integration of signatures reveals novel signaling pathways involved in the pathophysiology of cancer [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr A4." @default.
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- W2039441350 date "2012-07-01" @default.
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- W2039441350 title "Abstract A4: Two dimensional chemical interrogation of oncogenic systems and multi-omics integration of signatures reveals novel signaling pathways involved in the pathophysiology of cancer" @default.
- W2039441350 doi "https://doi.org/10.1158/1538-7445.csb12-a4" @default.
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