Individual tumour cells display diverse functional behaviours in terms of proliferation rate, cell-cell interactions, metastatic potential and sensitivity to therapy. Moreover, sequencing studies have demonstrated surprising levels of genetic diversity between individual patient tumours of the same type. Tumour heterogeneity presents a significant therapeutic challenge as diverse cell types within a tumour can respond differently to therapies, and inter-patient heterogeneity may prevent the development of general treatments for cancer. One strategy that may help overcome tumour heterogeneity is the identification of tumour sub-populations that drive specific disease pathologies for the development of therapies targeting these clinically relevant sub-populations. Here, we have identified a dye-retaining brain tumour population that displays all the hallmarks of a tumour-initiating sub-population. Using a limiting dilution transplantation assay in immunocompromised mice, label-retaining brain tumour cells display elevated tumour-initiation properties relative to the bulk population. Importantly, tumours generated from these label-retaining cells exhibit all the pathological features of the primary disease. Together, these findings confirm dye-retaining brain tumour cells exhibit tumour-initiation ability and are therefore viable targets for the development of therapeutics targeting this sub-population.

Unless diagnosed early, many adult cancers remain incurable diseases. This is despite an intense global research effort to develop effective anticancer therapies, calling into question the use of rational drug design strategies in targeting complex disease states such as cancer. A fundamental challenge facing researchers and clinicians is that cancers are inherently robust biological systems, able to survive, adapt and proliferate despite the perturbations resulting from anticancer drugs. It is essential that the mechanisms underlying tumor robustness be formally studied and characterized, as without a thorough understanding of the principles of tumor robustness, strategies to overcome therapy resistance are unlikely to be found. Degeneracy describes the ability of structurally distinct system components (e.g. proteins, pathways, cells, organisms) to be conditionally interchangeable in their contribution to system traits and it has been broadly implicated in the robustness and evolvability of complex biological systems. Here we focus on one of the most important mechanisms underpinning tumor robustness and degeneracy, the cellular heterogeneity that is the hallmark of most solid tumors. Based on a combination of computational, experimental and clinical studies we argue that stochastic noise is an underlying cause of tumor heterogeneity and particularly degeneracy. Drawing from a number of recent data sets, we propose an integrative model for the evolution of therapy resistance, and discuss recent computational studies that propose new therapeutic strategies aimed at defeating the adaptable cancer phenotype.

Whilst elevation of a nasoseptal flap in endoscopic surgery of the anterior skull base engendered significant clinical deterioration on examination post-operatively, quality of life outcomes showed that no such deterioration was subjectively experienced by the patient. In fact, there was significant nasal airway improvement following nasoseptal flap reconstruction.