Development of µPepArray as a Powerful Molecular Tool for Proteomic Profiling of Cellular Signaling Proteins (CSPs) of Pancreatic Cancer – Interrogate CSP Variations Induced by the Treatment of Tyrosine Kinase Inhibitors (TKIs)

Hanry Vo1, Celise Robertson1, Ruijuan Zhu2, Ailing Hong2, Xiaochuan Zhou2, Xiaolian Gao1
1 Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, USA.
2 LC Sciences, Houston, TX 77054

It is well accepted that molecular profiling of cellular proteins or nucleic acids can offer answers to courses of diseases and underlined connections of pathogenic molecules, and thus, pointing out therapeutic targets. However, protein profiling, especially at the cellular level of protein profiling has been challenging. There is only limited choices to allow systematic investigation of cellular protein activities, such as their responses, i.e., sensitive, responsive or nonresponsive or resistant, to therapeutic treatment. This presentation reports peptide microarray chip (PepArray) technology developed as a powerful molecular tool for proteomic profiling of Cellular Signaling Proteins (CSPs) to interrogate CSP variations in pancreatic cancer induced by treatment of a new generation of anti-cancer therapies, i.e., tyrosine kinase therapeutics (TKls). PepArray chips encodes receptor kinase protein (RTK) interactions with phosphotyrosine (pY) motif binding domain proteins, revealing signaling network activities, which are translated into clinic relevant information valuable for therapeutic treatment. Examples of cellular protein profiling of pancreatic cancer treated with three generations of small molecule tyrosine kinase (EGFR) inhibitors (TKis): Erlotinib (TarcevaTM); Afatinib (Gilotrif TM); and the 2016 FDA approved AZD9291 (TagrissoTM) will be demonstrated. Our PepArrayTMs tudies revealed protein profiles as molecular signatures of the cellular conditions through proteins of commonly or differentially expressed. The Proteomic profiles of pancreatic cancer cells revealed 80 signaling proteins implicated in 39 cancer related pathways under Erlotinib treatment; while 135 signaling proteins implicated in 38 cancer related pathways under Afatinib treatment; and 78 signaling proteins associated with 39 cancer related pathways under AZD9291 treatment. Such information about functional cellular proteins provided valuable molecular signature, which reflect cancer status to allow assessment of effectiveness of cancer treatment, i.e., sensitive vs insensitive, responsive vs resistant. PepArray proteomic and signaling pathway results thus hold clinical significance in identifying molecular markers in therapeutic treatment of pancreatic cancer, and the various cancers, and in the cancer therapeutic strategy including monitoring and predicting of therapeutic effectiveness, will lead to a strong molecular basis for application of precision medicine to greatly benefit human health and wellness.

Phosphopeptide Arrays

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