ONCOGENIC SIGNALLING OF CANCER DRIVERS - CONTEXT MATTERS
Günter Schneider, Marc Schmidt-Supprian, Roland Rad and Dieter Saur. (14-11-2016).Nature Reviews Cancer
Research Area C
How can we treat cancer more effectively? Traditionally, tumours from the same anatomical site are treated as one tumour entity. This concept has been challenged by recent breakthroughs in cancer genomics and translational research enabling molecular tumour profiling. The identification and validation of cancer drivers, which are shared between different tumour types, spurred the new paradigm to target driver pathways across anatomical sites by off-label drug use, or within so called “basket or umbrella trials”, assuming that findings in one tumour entity can be extrapolated to all others. Recent clinical and preclinical studies suggest however, that this assumption is not generally valid due to tissue- and cell type-specific differences in tumourigenesis and the organization of oncogenic signalling pathways. In this Opinion article, we focus on the molecular, cellular, systemic and environmental determinants of organ-specific tumourigenesis and mechanisms of context-specific oncogenic signalling outputs. Investigation, recognition and in-depth biological understanding of these differences will be vital for the design of next-generation clinical trials and the implementation of rational molecularly guided cancer therapies in the future.