Alterations in chromatin dynamics are relevant to cancer initiation and progression. On page 669, Alea A. Mills discusses the polycomb and trithorax protein complexes that repress or promote gene expression, respectively. The balance between these complexes is skewed in cancer cells, partly through the inappropriate methylation of histones. On page 721, Ali Shalitifard and colleagues present their current model of how the mammalian trithorax homologue, mixed lineage leukaemia (MLL), subverts gene expression in acute myeloid and acute lymphoid leukaemias. The insights gained from this model might allow the development of targeted agents in the treatment of these leukaemias.

The development of successful targeted drugs requires a precise knowledge of the mechanism of action of the protein or gene target. Pancreatic cancer is one of many cancers for which targeted drugs are desperately needed, and on page 683 John P. Morris, Sam C. Wang and Matthias Hebrok discuss the function of KRAS in the development of pancreatic ductal adenocarcinoma (PDAC). Mouse models that precisely recapture the human disease have been difficult to develop, although recent, more accurate models have indicated that a complex interplay between KRAS mutation and the subversion of the Wnt and Hedgehog signalling pathways is required in the initiation and progression of PDAC. Identifying additional genes and signalling pathways mutated in this and other cancers would also be of use for drug development; on page 696 Nancy A. Jenkins and Neal G. Copeland discuss the use of transposons, such as Sleeping Beauty, in mutating and identifying genes that cooperate in the generation of specific cancers.

All four of these articles highlight the different ways research is progressing to identify new and effective treatments for specific cancers.