Bioinformática aplicada ao desenvolvimento de estratégias de prognóstico e tratamento do câncer: estudos na prospecção de alvos terapêuticos, antígenos tumorais e na dinâmica de resposta a drogas

Abstract

Essentially, cancer research is a field that covers several branches, which expanding from basic to translational research, including cancer characterization, as well as, clinical trials and therapeutic development. Regardless, the cancer research has been focusing on cancer diagnosis, prognosis, treatment and, ultimately into the patient cure. In this context, the cancer bioinformatics can be defined as a powerful resource by integrating public data and, consequently, allowing the advancement of clinical applications. For instance, into the development of approaches to treat cancer, such as drug discovery and, recently into the immunotherapeutic strategies. In this work, we present distinct approaches to understand the cancer biology focusing on cancer treatment and, mainly, into prognosis prediction. Furthermore, all chapters cover different aspects into clinical applications, such as survival outcome prediction, opportunities for new immunological treatment, and drug resistance. The first chapters’ present extensive gene catalogs associated with i) cell surface markers, and ii) cancer/testis antigens (CTAs). Furthermore, we discuss the effect of gene signatures into prognosis status. As result, we present three-gene signatures associated with poor prognosis in breast cancer patients. On another hand, also have been shown a discussion about the development of new immunotherapy strategies based on multiple-CTAs vaccines. Particularly, we have shown how the CTAs signatures composed by HEATR9, INSL3, GTSF1L, and HSF5 are associated with good prognosis status in patients with melanoma. Finally, we present a methodology focusing on posttranscriptional regulation that integrates genotype information, expression data, and drug concentration to evaluate the treatment resistance/sensitivity using cell-line/patient data. In conclusion, were presented three independent approaches to improving cancer treatment, that can be used by combining or not the cell surface prognosis markers, drug response predictor and cancer vaccines. Also, as other important products were produced two international articles and, currently, an in-progress patent.