Identification of predictive molecular markers for cancer progression, response to therapy and disease outcome

The primary aim of the proposed project is to identify alterations in gene sequences, expression levels and protein structure or function that could be successfully used as predictive molecular markers of cancer progression, response to treatment and disease outcome. To achieve this goal we have designed two experimental approaches: hypothesis and non hypothesis driven approach. The objective of the first approach is a comprehensive analysis of key molecules involved in PI3K/Akt/mTOR signaling pathway at DNA, RNA and protein level in sets of postoperative tumour samples. This line of research should acknowledge the hypothesized role of PI3K/Akt/mTOR signaling pathway in cancer progression and, specifically, in acquiring resistance to chemotherapy and reveal potential markers. Non hypothesis driven approach is based on the screening of the whole genome through extensive analysis of paired tumour and normal tissue samples using AP-PCR, a DNA fingerprinting technique. By this approach we expect to identify novel genes whose alteration was not previously associated with cancer progression and resistance to therapy. Parallel to experimental research, clinical studies will be conducted and correlated with identified molecular markers with the aim to determine therapy modality outcome (chemotherapy, radiotherapy and surgery). Using various biophysical models we expect to access high-probability therapy response prediction for a specific tumour type based on molecular markers.