Research Highlights in 2017

Alvarez, Sviderskiyet al. have identified a pathway that allows primary lung tumour cells or lung metastatic breast tumour cells to survive in the high oxygen concentrations present in the lung.

Two new papers provide insight into the future treatment of mature T cell cancers.

The gut microbiome can modulate the clinical response to anti-programmed cell death protein 1 (PD1) immunotherapy in patients with solid tumours.

The importance of 'Warburgian' metabolism in cancer is an increasingly disputed topic. By studying cancer metabolism in patients and mouse models, Faubertet al. now show that lactate is used as a respiratory fuel in non-small-cell lung cancer in vivo.

New research published inNaturenow demonstrates that immune checkpoint blockade can alleviate hepatocellular carcinoma progression in patients with nonalcoholic steatohepatitis (NASH) by inhibiting immunosuppressive immunoglobulin A-producing cells in the liver.

An embryonic avian model recapitulates the early stages of tumorigenesis and metastases seen in patients with neuroblastoma.

Melloet al. analysed the effects of various p53 transactivation domain mutants in pancreatic ductal adenocarcinoma and uncovered a crucial tumour-suppressive pathway in which p53 mediates inhibition of the transcriptional co-activator YAP.

A modular synthetic RNA-based gene circuit has been developed to program tumour cells to express a combination of immunomodulators to improve the specificity and efficacy of cancer immunotherapy.

Sympathetic nerves associate with tumours and regulate the tumour microenvironment. How this innervation promotes tumorigenesis is unclear. A new study in Scienceshows that β-adrenergic signalling controls tumour growth by promoting tumour angiogenesis, through the regulation of vascular metabolism.

Konget al. report a mechanism that underlies tumour 'drug addiction' in melanoma cell lines and mouse models involving an ERK2-dependent phenotype switch, which might have clinical implications for the use of alternating treatment strategies with targeted therapies.

A recent study shows that smoking-induced epigenetic changes in lung epithelium occur even before malignant transformation, and sensitize the cells to allow a single key oncogenic event to initiate the growth of a tumour.

Two studies have shown the potential of oncolytic viruses to reverse immunosuppression in the tumour microenvironment.

Zhanget al. report that CD8⁺tumour-infiltrating T lymphocytes exposed to a hypoglycaemic and hypoxic tumour microenvironment enhance PPARα signalling and fatty acid catabolism to partially preserve effector functions and increase the efficacy of immunotherapy in melanoma mouse models.

Using DNA barcoding, Lanet al. investigated the clonal evolution and dynamics of glioblastoma cells, and propose a model whereby proliferative heterogeneity is derived from stochastic fate decisions made by a homogeneous population of glioblastoma stem cells and their progeny.

Vitamin C supplementation has shown limited benefits in patients with solid tumours. Two studies report that vitamin C supplementation can reduceTet-dependent leukaemia progression in mice, supporting the concept of high-dose vitamin C supplementation in certain patients with haematological malignancies.

Although speckle-type POZ protein (SPOP) is the most frequently mutated gene in primary prostate cancer, its therapeutic implications are incompletely understood. Now, three studies describe mechanisms of resistance to bromodomain and extraterminal (BET) protein inhibitors in SPOP-mutated prostate cancer.

Both obesity and systemic inflammation promote cancer progression, although how obesity-associated inflammation affects cancer metastasis is poorly understood. Quailet al. now show that obesity induces cytokines that stimulate lung neutrophilia in mice, thereby promoting breast cancer metastasis.

Reporting inNature, the team led by Haining has identified that deletion of Ptpn2, among other genes, in tumour cells makes them more susceptible to PD1 inhibitors.

Since mesenchymal-like properties in cancer cells are often associated with therapy resistance, Viswanathanet al. explored vulnerabilities of these cells. They identified an enzyme of the lipid peroxidase pathway, inhibition of which caused ferroptosis in a range of cancer types.

A new study has looked at the evolutionary origins of lymphatic and distant metastases in human colorectal cancer and found that, in most cases, cancer spread to lymph nodes is not a precursor for seeding of cancer cells to other organs.