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Nature Reviews Cancer


Tumour vaccines: Personal training by vaccination


Two groups have shown that personalized, neoantigen-based tumour vaccines elicit effective T cell responses in patients with advanced melanoma, leading to favourable clinical outcomes. Combination with checkpoint blockade can be of additional benefit.

Pancreatic cancer: iExosomes target the 'undruggable'


Kamerkar et al. have engineered exosomes that target KRASG12D (iExosomes) and have demonstrated the specificity and efficacy of iExosomes in targeting oncogenic KRAS in mouse models of pancreatic cancer.

Therapeutic resistance: Transcribing patterns of resistance


Shaffer et al. analysed resistance in melanoma at the single-cell level and found that non-genetic, transcriptional variability in rare cells can predict the eventual emergence of drug resistance.

Epigenetics: Tumour suppressive HIF2α


Westerlund et al. found that combining the DNA demethylating drug 5-aza-deoxycytidine with the differentiation-promoting therapy retinoic acid inhibited tumour growth and prolonged survival in mouse xenograft models of high-risk neuroblastoma. This treatment resulted in high hypoxia-inducible factor 2α (HIF2α) levels but not HIF1α, and

Tumour immunology: Feeding frenzy


Tumour cells are thought to avoid being phagocytosed through expression of the 'self' marker CD47, which ligates the macrophage receptor SIRPα. Alvey et al. investigated the potential of SIRPα-inhibited bone marrow-derived macrophages, primed with tumour-targeting antibodies, to clear tumours in vivo. Systemic injection

Tumour immunology: Tumours copy to escape


How tumours escape the immune system is not well defined. Nirschl et al. show that immune phagocytes in human melanoma share a physiological gene signature, which co-enriches and correlates with interferon-γ (IFNγ)-directed gene transcripts, and which is induced across multiple human cancers. Suppressor of

Leukaemia: Multiple origins of relapse


The origin of relapse in acute myeloid leukaemia (AML) is thought to be due to drug-promoted mutagenesis or to the selection of drug-resistant cells. Shlush et al. provide evidence for the latter and propose at least two distinct patterns of relapse in AML. In

Immunotherapy: Keeping breast cancer in check


Nolan et al. show that triple-negative breast cancers with BRCA1 mutations are immunogenic and susceptible to treatment with a combination of two checkpoint inhibitors and chemotherapy.

Chemotherapy: Neutrophils deliver the goods


Neutrophils carrying liposomes that contain the antimitotic drug paclitaxel can penetrate the brain and suppress the recurrence of glioma in mice, thereby significantly improving survival.

Neuroblastoma: Tumours get super-enhanced


Van Groningen et al. unravel the epigenetic nature of intratumoural heterogeneity in neuroblastoma, which comprises both lineage-committed adrenergic cells and undifferentiated mesenchymal cells that are defined by unique super-enhancer transcriptional networks and gene expression signatures.

Epigenetics: Therapy-induced transcription is cryptically widespread


A new study demonstrates that DNA methyltransferase inhibitors and histone deacetylase inhibitors induce widespread cryptic transcription from transposable elements that may contribute to cancer immunogenicity.

Microenvironmental regulation of tumour angiogenesis


Tumours display considerable variation in the patterning and properties of angiogenic blood vessels, as well as in their responses to anti-angiogenic therapy. Angiogenic programming of neoplastic tissue is a multidimensional process regulated by cancer cells in concert with a variety of tumour-associated stromal cells and

Novel insights into mesothelioma biology and implications for therapy


Malignant mesothelioma is a universally lethal cancer that is increasing in incidence worldwide. There is a dearth of effective therapies, with only one treatment (pemetrexed and cisplatin combination chemotherapy) approved in the past 13 years. However, the past 5 years have witnessed an exponential growth

Fragile sites in cancer: more than meets the eye


Ever since initial suggestions that instability at common fragile sites (CFSs) could be responsible for chromosome rearrangements in cancers, CFSs and associated genes have been the subject of numerous studies, leading to questions and controversies about their role and importance in cancer. It is now

Drugging the 'undruggable' cancer targets


The term 'undruggable' was coined to describe proteins that could not be targeted pharmacologically. However, progress is being made to 'drug' many of these targets, and therefore more appropriate terms might be 'difficult to drug' or 'yet to be drugged'. Many desirable targets in cancer