Opinion in 2014

Potential drug–drug interactions mediated by ATP-binding cassette (ABC) and solute carrier (SLC) transporters are of clinical and regulatory concern, but the endogenous function of these drug transporters is unclear. Nigam describes the evidence that these transporters transport diverse endogenous substrates and could potentially be important in remote communication. Understanding such functions could clarify the roles of these transporters in disease and in drug–metabolite interactions.

Caloric restriction can promote health and extend the lifespan of model organisms, and diverse classes of compounds that mimic the biochemical and functional effects of caloric restriction have attracted considerable interest as potential pharmacotherapies for diseases such as diabetes and obesity. Kroemer, Madeo and colleagues propose a unifying definition of caloric restriction mimetics as agents that induce autophagy by promoting protein deacetylation, which could have implications for their development as drugs.

Over the past decade, cancer stem cells have emerged as the centerpiece of cancer research, having a major role in resistance to conventional therapy and in the metastatic spread of tumours. The authors discuss the biological complexity of this subpopulation of cells within tumours and explore novel means to tackle them therapeutically based on our current understanding.

Agents that target tumour-supportive cellular machineries, such as the proteasome, heat shock protein complexes and proteins involved in chromatin modifications, are emerging as a new wave of anticancer drugs. Here, Dobbelstein and Moll provide their perspective on the advantages and limitations of these agents compared with established drugs that target DNA replication or signalling proteins such as kinases.