Research Highlights in 2015

Petersonet al. report that basal cell carcinomas primarily arise from stem cells within hair follicle and touch dome epithelia, and that cutaneous nerves promote tumorigenesis.

Two papers report on the preclinical efficacy of targeting the menin–MLL interaction in MLL-translocation-associated leukaemias and in prostate cancer.

The BRG1 catalytic subunit of the chromatin remodelling SWI/SNF complex has context-dependent functions during different stages of pancreatic ductal adenocarcinoma development from intraductal papillary mucinous neoplasia, and bromodomain and extraterminal inhibitors might be therapeutically beneficial in this subtype of pancreatic cancer.

The efficacy of dendritic cell vaccines can be improved in patients with glioblastoma by pre-conditioning the vaccine site with the tetanus/diphtheria toxoid.

Dual immune checkpoint blockade combined with radiation promotes effective antitumour immunity through distinct mechanisms.

Two papers inNature Geneticsreport on the role of stromal cells, especially cancer-associated fibroblasts, in poor-prognosis colorectal cancer.

Sottorivaet al. propose a model by which colorectal tumours evolve, which generates different types of spatial intratumoural heterogeneity.

Marzecet al. have described a new telomere-dependent mechanism by which genomic instability and chromosomal translocations can be induced in cancer cells that use alternative lengthening of telomeres for telomere maintenance.

Polaket al. have found that the mutation profile of a given cancer can be predicted from the epigenomic signature of the cell type from which that cancer was most likely to have originated.

Ortmann and Kentet al. show that the order of acquisition of Janus kinase 2 (JAK2) mutations and tet methylcytosine dioxygenase 2 (TET2) mutations in myeloproliferative neoplasms can affect tumour cell biology and clinical phenotypes.

Alberto Mantovani and colleagues have found that loss of a regulator of the complement cascade, penatraxin 3 (PTX3), accelerates tumour development in mice owing to a complement- and macrophage-mediated immune response.

Two studies have shown that DNA polymerase-θ (POLQ) promotes an alternative form of non-homologous end-joining (alt-NHEJ) and suppresses homologous recombination (HR) in mammalian cells. The activity of alt-NHEJ is essential for the survival of cells deficient in HR.

Stites and Trampontet al. used mathematical modelling with verification in cells and cancer genome data to understand the effects of weakly activating RAS mutations. They found that pairs of mutations within the RAS pathway might be able to act together to create a selective advantage in human tumours.

This study describes a novel approach to increase blood vessels in tumours to enhance drug delivery, uptake and metabolism.

Two studies have examined how manipulation of energy availability by cancer cells, mediated by changes in microRNAs (miRNAs), can fuel metastatic colonization.

Two studies offer new possibilities to fight BRAF inhibition resistance.

Madsenet al. have delineated the roles of components of the striatin-interacting phosphatase and kinase (STRIPAK) complex in cancer cell migration and metastasis, which may explain why some of these proteins are overexpressed or mutated in cancer.

Yodaet al. have shown that mutations in G protein-β (Gβ) subunits occur in haematological malignancies and can transform cells. Mutant Gβ can also confer resistance to different therapeutic kinase inhibitors.

Tumour cells without mitochondrial DNA acquire mitochondria from host cells to re-establish respiration and tumour-initiating efficacy.

Three papers report on the use of acetate as a nutrient in tumour cells undergoing metabolic stress.