Research Highlights in 2016

Schereret al. show that analysis of circulating tumour DNA can provide prognostic information and predict relapse in patients with diffuse large B-cell lymphoma.

Two papers have shown in mouse tumour models that targeting PI3Kγ in myeloid cells can reduce immune suppression and increase the efficacy of immune checkpoint inhibitors.

Skauet al. demonstrate that the actin nucleating protein FMN2 generates a perinuclear actin and focal adhesion-based structure to protect the nucleus from damage during cell migration through confining 3D microenvironments.

Mathias Wenes and colleagues have studied metabolic changes in tumour associated macrophages (TAMs) and found that specific alterations of mTOR regulation through regulated in development and DNA damage response 1 (REDD1) results in defective blood vessel formation and increased metastasis.

A paper inNaturedescribes a highly specific and potent small molecule inhibitor of MCL1 that has single-agent activity and good tolerability in several cancer models.

Two studies have revealed two possible mechanisms that might explain why VEGF inhibition can be rendered ineffective

Two papers examine the influence of different stem cell characteristics on tumorigenesis in an organ-specific and age-associated manner, continuing the debate on the influence of intrinsic and extrinsic factors on cancer risk.

An analysis of pancreatic ductal adenocarcinoma genomes indicates that many of these tumours undergo polyploidization and chromothripsis, leading to rapid acquisition of genetic changes required for tumour progression.

A subset of cancer cells is dependent on a large, stable multi-protein complex called the epichaperome for survival under conditions of stress.

Daillèreet al. have identified two bacterial species that mediate systemic and tumour-infiltrating T cell responses associated with the antitumour efficacy of the chemotherapy drug cyclophosphamide.

Boice, Salloum, Mourcinet al. show that HVEM is an important tumour suppressor in lymphomas and that direct delivery of a soluble HVEM peptide using engineered T cells might be therapeutically beneficial.

Two studies have looked at the roles of fatty acid synthesis and oxidation, and their therapeutic potential, in cancer.

Cell differentiation blockade in the early stages of AML can be overcome by inhibiting dihydroorotate dehydrogenase

Brand and colleagues show that increased tumour lactate dehydrogenase A (LDHA)-mediated lactic acid production dampens activation and cytokine production of infiltrating T and natural killer (NK) cells allowing tumours to escape immune detection and promoting tumour growth.

Mayers, Torrenceet al. show that lung tumours driven by oncogenic KRAS and loss of p53 depend on branched-chain amino acid metabolism, whereas pancreatic tumours driven by the same genetic defects do not.

Three studies demonstrate the preclinical potential of a novel class of hypoxia-inducible factor 2α (HIF2α) antagonists in the treatment of von Hippel–Lindau (pVHL)-deficient clear cell renal cell carcinoma.

Acidosis reprograms the metabolism of cancer cells toward fatty acid oxidation by downregulating acetyl-CoA carboxylase ACC2 through histone deacetylation

Sousaet al. demonstrate a reciprocal metabolic cross-talk between pancreatic stellate cells (PSCs) and pancreatic tumour cells whereby secreted autophagic alanine from PSCs is taken up by tumour cells and used as an alternative carbon source to support tumour growth.

Chaeet al. show that mitochondrially-localized AKT phosphorylates pyruvate dehydrogenase kinase 1 (PDK1) to promote tumour cell growth and survival in hypoxic conditions.

Two papers show that specific diets or pharmacological agents that mimic fasting inhibit tumour growth in combination with chemotherapy through effects on the immune system.