Tackling the cancer signal transduction “labyrinth”: a combinatorial use of biochemical tools with mathematical models will enhance the identification of optimal targets for each molecular defect.

Unraveling cancer-associated molecular defects is crucial for further pharmacological targeting. Although novel techniques are being developed to elucidate genomic, proteomic, and transcriptomic alterations, the map of protein interactions and aberrations in normal but also in malignant cells is still obscure. It has been recently shown that many of the events in signaling cascades might be revealed using mathematical models. Transcriptional regulation still represents the main obstacle for the design of truly molecularly-targeted agents, mainly due to its enormous plasticity and heterogeneity in cells and tissues. Systematic mapping of signaling networks and application of new computational algorithms will reinforce the use of novel research tools in this venue. The case of epidermal growth factor receptor family proteins and their intracellular cross-talk interactions and downstream molecules is used as a representative paradigm.