Research Highlights in 2018

Roerink et al. have used organoids derived from multiple single cells of colorectal cancers from three patients as well as from normal colorectal epithelium of the same patients to comprehensively study intratumoural heterogeneity.

Wang et al. have developed a diagnostic tool (based on the widely used Papanicolaou (Pap) test) to detect endometrial and ovarian cancer in patients by using PCR-based analyses of genetic mutations and aneuploidy.

Han et al. have identified a new tumour-induced immune cell population in the spleen that can promote tumour growth through production of the neurotrophic factor artemin.

Ferrari de Andrade et al. find that monoclonal antibodies that prevent shedding of MICA and MICB from tumour cells can restore antitumour immunity by natural killer cells.

Whether lymph node metastases can be a source of cancer cells for distant metastases has been debated. Now, two studies have used mouse models to show that tumour cells can colonize distant organs by invading lymph node blood vessels.

Using clinical tissue specimens and mouse models of breast cancer, Incio et al. show that obesity promotes the upregulation of interleukin-6 and fibroblast growth factor 2 in the tumour microenvironment, which confer resistance to anti-vascular endothelial growth factor therapy.

In a new study, researchers show that basal-like breast cancer can be converted into the luminal subtype by inhibiting platelet-derived growth factor (PDGF)-CC signalling in the tumour microenvironment, thereby potentially broadening treatment options for oestrogen receptor-negative breast cancer patients.

Good et al. use deep phenotypic single-cell analyses and machine learning to identify developmentally dependent cell signalling states in B cell precursor acute lymphoblastic leukaemia that are predictive of relapse.

Deregulation of the COMPASS-like complex, via loss ofKDM6A in females and loss of both KDM6A and its Y chromosome homologue UTYin males, is important for activation of oncogene-associated super-enhancers and the development of pancreatic adenocarcinoma of the squamous subtype.

Wang, C., Wang, J. et al. show that local injection of a hydrogel scaffold degraded by reactive oxygen species in the tumour microenvironment releases chemotherapy and an immune checkpoint inhibitor with kinetics that increase antitumour responses.

A paper inNature Medicinedescribes a novel, orally available splicing modulator that preferentially kills cancer cells with mutations in splicing factors in culture and in mouse models.

Activation of TGFβ signalling in invasive margins of metastatic tumours can contribute to T cell exclusion and reduced immune checkpoint therapy response. Inhibition of TGFβ in non-responders can potentially help to improve outcomes in these patients.

Xieet al. show that senescence-associated DNA methylation changes evolve independently of stochastic tumour-associated methylation changes and that a subset of commonly methylated genes with the highest gains are associated with early tumorigenesis and ageing.

A recent study published inNature Cell Biologyhas shown that tumour spheres that maintain an inverted epithelial architecture originate from primary colorectal cancers and can collectively invade the peritoneum, initiating metastasis.

Liet al. report the development of 'DNA nanorobots' carrying a thrombin protease payload that induce coagulation and necrosis at the tumour site, illustrating their therapeutic potential as drug delivery systems.

Data presented by Bakhoum, Ngo et al. suggest that chromosomal instability can promote metastasis through a cGAS–STING-dependent response to cytosolic DNA.

A subset of cancer-associated firboblasts, defined by the presence of the cell surface markers CD10 and GPR77, promotes tumour formation and chemoresistance by providing a niche for cancer stem cells.

Mitogen- and stress-activated kinase 1 (MSK1) has been identified as an epigenetic modulator of luminal gene expression in breast cancer, maintaining latency of bone micrometastases.

Two studies have shown that oncolytic virus treatment prior to surgery can prime the tumour immune microenvironment for subsequent immune checkpoint inhibition and lead to better outcomes in preclinical models of breast and brain cancers.

The fusion gene consisting of fibroblast growth factor receptor 3 and transforming acidic coiled-coil-containing protein 3 is oncogenic and present in a small cancer subset. Frattini et al. have identified that this fusion gene drives peroxisomal and mitochondrial biogenesis.