Research Highlights in 2014

A screening platform using cell cultures derived from tumour biopsy samples identifies drug combinations that are effective in treating tumour resistance.

This paper finds that levels of histone H3 lysine 79 (H3K79) methylation affect the level of gene expression through the AF10–DOT1L complex, with implications for acute myeloid leukaemia therapy.

Elsa Flores and colleagues have found that a pancreatic hormone, amylin, induces regression ofTrp53-null tumours.

Seven new studies advance our understanding of immune checkpoint blockade and highlight an approach for developing personalized cancer vaccines.

Data from three recent papers suggest that alterations of super-enhancers in cancer cells can promote oncogene expression and therapeutic resistance in some cases. Proteins that promote transcription from super-enhancers might be viable therapeutic targets.

The induction of a type I interferon response in cancer cells is linked to the efficacy of certain chemotherapies.

Two papers have revealed new roles of exosomes in cancer progression: as mediators of therapeutic resistance signals from the stroma and as microRNA generators.

Two papers describe the evolution and heterogeneity of non-small-cell lung cancers by carrying out sequencing of samples from multiple tumour regions, with interesting conclusions and raising challenges for the future.

Falleret al. have shown that intestinal cells lacking APC require mTOR complex 1 (mTORC1) signalling for tumour formation, but that it is translation elongation controlled by mTORC1 (and not translation initiation) that is important in these cells.

Cheunget al. show that the protein encoded by a common mutation in PIK3R1(the p85α subunit of PI3K) has neomorphic functions, including nuclear localization and the activation of ERK and JNK signalling, which can promote tumour cell proliferation and survival. Furthermore, tumours expressing this mutation are sensitive to MEK and JNK inhibitors.

Brozet al. identify a rare intratumoral CD103⁺dendritic cell population that stimulates cytotoxic T cells.

Several tumour-promoting roles of cathepsin Z (CTSZ) in pancreatic neuroendocrine tumours (PanNETs) depend on its RGD motif, and CTSZ derived from tumour cells or tumour-associated macrophages has different functions.

Xuet al. have identified the cell of origin of retinoblastoma and the cell type-specific circuitry that these tumour cells rely on.

LeBleuet al. show that the metabolism of migratory and circulating tumour cells is different to that of primary tumour cells and this difference enables migration and metastasis.

Blood vessel branching during tumour angiogenesis is mediated by the formation of podosome rosettes.

Wanget al. show differential requirements for the glycolytic enzymes pyruvate kinase M2 and lactate dehydrogenase A in maintaining haematopoietic stem cells and progenitor cells. Although this difference does not seem to apply to leukaemias derived from these two different cell populations, leukaemia cells are more sensitive to glycolysis inhibition than normal cells.

Chenet al. have shown that growth of isocitrate dehydrogenase 1 (IDH1)-mutant gliomas is promoted by expression of glutamate dehydrogenase 2 (GLUD2) protein.

Vagal innervation promotes tumorigenesis via WNT signalling mediated by muscarinic acetylcholine receptor 3 (M3R) in gastric cancer. Denervation, therefore, might represent a feasible strategy to control this disease.

A new study has shown that intratumoural injection of attenuated bacteria can reduce tumour volume.

Ganemet al. elucidate the mechanisms underlying cell cycle arrest in tetraploid cells in vitro and in vivo.