Ovarian cancer (OvCa) stands out among gynecological malignancies for being one of the most lethal and difficult to diagnose. Like other cancers, the OvCa arises of progressive accumulation of cellular changes promoted by mutations in cell genome that, consequently, alter the complex pathways regulating cell that respond to internal factors, such as genetic reprogramming, or external, such as growth factors. In this project it will evaluated the influence of several signaling mechanisms and pathways involved in the development and modulation of biomarkers and biomarker candidates for OvCa. OvCa cell lines will be stimulated to tumor progression or metastasis with growth factors and cytokines and the response in terms of proteins concentration, will be determined by targeted proteomics strategy based on mass spectrometry (Selected Reaction Monitoring - SRM). In this way, several molecules selected and involved with OvCa will be simultaneously quantified and correlated with their corresponding modulating signaling pathways. From these results, and also from recent proteomic data obtained in our laboratory during induction of epithelial-mesenchymal transition in OvCa cell lines, signaling pathway will be selected for inhibition studies using specific inhibitors or interference RNA, and thus confirm the modulation of these proteins during the cellular models of tumor progression. Some of these molecules will also be investigated in tumor fluid (ascito) obtained from patients by immunodetection techniques and SRM in order to compare, validate and stratify data obtained in vitro. As a result of this study, we hope to expand our understanding of biomarkers known in OvCa and, especially, identifying and verifying potential new biomarkers and protein signatures, thereby contributing to the diagnosis and therapy of this important malignancy.
News published in Agência FAPESP Newsletter about the scholarship: