Research Highlights in 2015

A paper published inNature Medicinereports on the results of treating patients with multiple myeloma with engineered T cells that recognise the cancer—testis antigen NY-ESO-1.

Two papers published inNature Geneticshave reported whole-genome and whole-exome sequencing of paired Barrett oesophagus and oesophageal adenocarcinoma (EAC) samples, providing some insights into the development of EAC from its precursor lesion.

Alekseyenko, Walshet al. have discovered that NUT fusion proteins, which underlie the development of the aggressive squamous cell cancer NUT midline carcinoma, localize to very large hyperacetylated domains within chromatin, which they term 'megadomains', leading to aberrant transcriptional programmes that promote tumorigenesis.

Lévyet al. show that autophagy is abnormally active during colorectal cancer development and is required for cancer cell metabolism.

A paper published inMolecular Cell indicates that the production of ketones can promote the BRAF^V600E–MEK–ERK oncogenic pathway and identifies a potential Achilles' heel.

Mohammedet al. have examined the functional interactions between oestrogen receptor-α (ERα) and progesterone receptor (PR) in mouse and human breast tumours. They found that activation of PR changes the pattern of ERα chromatin binding, resulting in the expression of antiproliferative genes.

A paper inNatureidentifies glypican 1 as a marker of circulating exosomes derived from pancreatic ductal adenocarcinoma (and from some breast cancers) that could be an effective biomarker for early diagnosis and treatment monitoring.

Activation of pannexin 1 channels promotes the survival of disseminated cancer cells in the microvasculature of metastasis target organs.

Inducible short hairpin RNA (shRNA)-mediated silencing of adenomatous polyposis coli (Apc) in the intestines of mice has revealed that APC loss is crucial for tumour maintenance even in the presence of other oncogenic mutations, and that re-expression of APC can restore normal crypt homeostasis.

Three papers now present different aspects of a similar story: altered splicing can lead to myelodysplastic syndrome (MDS) and even to progression to acute myeloid leukaemia (AML).

Coxet al. have shown that metastasis of certain breast cancers to bone can be driven by the enzyme lysyl oxidase (LOX), which induces bone lesions that provide a landing site for circulating tumour cells.

Zhuet al. find that the homing of multiple myeloma cells to the bone marrow is promoted by cyclophilin A–CD147 signalling between bone marrow endothelial cells and myeloma cells.

One way that MYC promotes lymphomagenesis is through maintaining correct pre-mRNA splicing.

Two recent studies add to the evidence supporting an important role for extracellular vesicles in promoting metastasis and provide a new technique for analysing these vesiclesin vivo.

Goodarziet al. find that small non-coding RNAs derived from the cleavage of tRNAs under hypoxic conditions can suppress metastatic progression.

Two different devices have been developed to deliver cancer drugs directly into tumoursin vivoto evaluate cell penetration, drug stability and effectiveness.

Hirataet al. used intravital imaging to characterize a surprising form of BRAF-V600E inhibitor resistance in melanoma.

Tumour cells coated with immunoglobulin G are able to induce an immune response in mice that causes tumour regression.

Liuet al. show that the mushroom-derived toxin α-amanitin, conjugated to antibodies against a tumour-specific biomarker, might be effective therapeutically (with minimal toxicity) for tumours that have hemizygous deletions of TP53 that also encompass POLR2A.

Gundemet al. sequenced a series of primary tumours and matched metastases from patients with metastatic prostate cancer; they showed that metastases are often seeded by multiple clones and that there are multiple paths of metastatic spreading.