Signaling and Chromatin Networks in Cancer Biology

Abstract In addition to diseases related to the cardiovascular system, cancer remains the most common morbidity in the developed world. Despite huge efforts by researchers, clinicians, and the industry, effective therapeutic targeting of malignancies remains challenging. Among the many features that characterize cancer cells, their ability to undergo dynamic and reversible transitions between multiple phenotypic states in adaptation to external signals represents the major hurdle in cancer therapy. This plasticity represents a powerful cellular program that enables cancer cells to naturally select for advantageous traits to circumvent cellular checkpoints and to evade cancer therapy. On the molecular level, cellular plasticity is controlled by several highly interconnected signaling pathways, which integrate extracellular signals of the tumor environment to a small cohort of transcription factors. These regulators control complex epigenetic mechanisms, such as modifications of chromatin-associated histones, to achieve widespread changes in gene expression required for the plastic phenotype of cancer cells. This chapter will summarize the most relevant molecular events that underlie and control cancer cell plasticity and illuminate how the understanding of these functional networks might impact cancer progression, therapy, and prognosis.