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The biological framework: translational research from bench to clinic.

The understanding of cellular signaling pathways in malignant tumors is an important aspect of cancer research and modern targeted therapy strategies. Growth factors and their receptors in particular are critical to modern cancer therapy research, because these factors control all phases of tumor development and metastasis. Most importantly, growth factors are responsible for cell survival under cytotoxic drugs and radiotherapy. These growth factor signaling pathways are composed of complex networks that have adapted to efficiently respond to certain disturbances, such as a single agent that targets one aspect of the pathway. Meanwhile, multiple insults to the pathway, such as combination therapy regimens, are known to be effective in shutting down these pathways and, consequently, killing the tumor cell. Research is currently under way to find new ways to exploit fragile aspects of oncogenic networks, such as uncommon, multiple perturbations that target essential hubs through immunotherapy, combinations of antibodies, heat shock protein inhibitors, or novel drug combinations. Complex growth factor signaling networks and novel methods to shut down these networks are described within a framework of engineering and mathematical concepts.