Understanding and exploiting cell signalling convergence nodes and pathway cross-talk in malignant brain cancer

In cancer, complex intracellular and intercellular signals constantly evolve for the advantage of the tumour cells but to the disadvantage of the whole organism. Decades of intensive research have revealed the critical roles of cellular signalling pathways in regulating complex cell behaviours which influence tumour development, growth and therapeutic response, and ultimately patient outcome. Most studies have focussed on specific pathways and the resulting tumour cell function in a rather linear fashion, partly due to the available methodologies and partly due to the traditionally reductionist approach to research. Advances in cancer research, including genomic technologies have led to a deep appreciation of the complex signals and pathway interactions operating in tumour cells. In this review we examine the role and interaction of three major cell signalling pathways, PI3K, MAPK and cAMP, in regulating tumour cell functions and discuss the prospects for exploiting this knowledge to better treat difficult to treat cancers, using glioblastoma, the most common and deadly malignant brain cancer, as the example disease. •The review discusses the role and interaction of MAPK and PI3K cell signalling pathways in brain cancer cells.•The review presents emerging evidence of the importance of the cAMP pathway in the context of cancer cell survival.•The review examines the possibility of targeting cell signalling hubs, exemplified by the transcription factor CREB.•Safer, more effective cancer treatment can be achieved by targeting specific, pivotal nodes, across multiple pathways.