Disruption of cell death signaling in cancer: impact on disease prognosis and response to therapy.

Disruption of cell cycle and apoptosis signaling pathways are key events during tumorigenesis, tumor progression and development of resistance against anticancer therapies. Thus, the analysis of functional alterations within these signaling cascades is of utmost importance for the understanding of resistance mechanisms, clinical outcome and risk-adapted treatment strategies. Key signaling pathways involved in the treatment resistance include the p53/p14ARF signaling complex and the mitochondrial apoptosis machinery. Apart from the direct genetic events, these signaling cascades are subject to epigenetic modulations implied by the tumor microenvironment.