Cancer

Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion

Nature Rev. Cancer - 17 May 2019 - 12:00am

Nature Reviews Cancer, Published online: 17 May 2019; doi:10.1038/s41568-019-0149-1

This Opinion article provides an overview of the mechanisms that regulate sensitivity to ferroptosis in cancer cells and how the modulation of metabolic pathways controlling ferroptosis might reshape the tumour niche, leading to an immunosuppressive microenvironment that promotes tumour progression.
Categories: Cancer

Tertiary lymphoid structures in the era of cancer immunotherapy

Nature Rev. Cancer - 15 May 2019 - 12:00am

Nature Reviews Cancer, Published online: 15 May 2019; doi:10.1038/s41568-019-0144-6

Tertiary lymphoid structures (TLSs) form outside of lymphoid tissues at sites of chronic inflammation, including tumours. This Review describes the evidence demonstrating that TLSs are critical for generating antitumour immune responses and are associated with better prognosis in certain cancer types. It also presents potential strategies aimed at inducing TLS neogenesis to improve clinical responses in poorly immunogenic cancers.
Categories: Cancer

Going to extremes: determinants of extraordinary response and survival in patients with cancer

Nature Rev. Cancer - 10 May 2019 - 12:00am

Going to extremes: determinants of extraordinary response and survival in patients with cancer

Going to extremes: determinants of extraordinary response and survival in patients with cancer, Published online: 10 May 2019; doi:10.1038/s41568-019-0145-5

For any given cancer type, there are patients who have exceptionally favourable or atypically poor responses to treatment and overall survival. This Opinion article outlines approaches to identify and study these patients at the extremes of the spectrum with a view to gain insights that will be applicable to the wider patient population.
Categories: Cancer

Prophylactic TNF blockade reduces autoimmune toxicity

Nature Rev. Cancer - 9 May 2019 - 12:00am

Prophylactic TNF blockade reduces autoimmune toxicity

Prophylactic TNF blockade reduces autoimmune toxicity, Published online: 09 May 2019; doi:10.1038/s41568-019-0152-6

In a study published in Nature, Perez-Ruiz et al. report that prophylactic tumour necrosis factor (TNF) blockade reduces gastrointestinal immune-related adverse events in mice treated with dual immune-checkpoint inhibition, providing a clear preclinical rationale for the clinical investigation of such strategies.
Categories: Cancer

E-selectin fills two needs for metastasis

Nature Rev. Cancer - 7 May 2019 - 12:00am

E-selectin fills two needs for metastasis

E-selectin fills two needs for metastasis, Published online: 07 May 2019; doi:10.1038/s41568-019-0151-7

Esposito et al. describe a mechanism for the simultaneous induction of mesenchymal-to-epithelial transition and stem cell traits in disseminating breast cancer cells in the bone, and provide therapeutic opportunities to prevent initiation of bone metastasis.
Categories: Cancer

The broken cycle: E2F dysfunction in cancer

Nature Rev. Cancer - 3 May 2019 - 12:00am

The broken cycle: E2F dysfunction in cancer

The broken cycle: E2F dysfunction in cancer, Published online: 03 May 2019; doi:10.1038/s41568-019-0143-7

Alterations of the cyclin-dependent kinase (CDK)–RB–E2F axis occur in virtually all cancers and result in heightened oncogenic E2F activity and uncontrolled proliferation. This Review discusses the activities of E2F proteins in cancer and therapeutic strategies to target this oncogenic pathway.
Categories: Cancer

Better safe than sorry: a potential prophylactic treatment for brain metastasis

Nature Rev. Cancer - 3 May 2019 - 12:00am

Better safe than sorry: a potential prophylactic treatment for brain metastasis

Better safe than sorry: a potential prophylactic treatment for brain metastasis, Published online: 03 May 2019; doi:10.1038/s41568-019-0150-8

Benbenishty et al. find that prophylactic administration of CpG-C, a Toll-like receptor 9 agonist, significantly reduces the development of brain metastasis in preclinical mouse models via the activation of microglial cells that kill and phagocytose the tumour cells.
Categories: Cancer

Macrophage manipulation

Nature Rev. Cancer - 2 May 2019 - 12:00am

Macrophage manipulation

Macrophage manipulation, Published online: 02 May 2019; doi:10.1038/s41568-019-0148-2

Macrophage manipulation
Categories: Cancer

Prioritizing synthetic lethal targets with functional genomics

Nature Rev. Cancer - 29 April 2019 - 12:00am

Prioritizing synthetic lethal targets with functional genomics

Prioritizing synthetic lethal targets with functional genomics, Published online: 29 April 2019; doi:10.1038/s41568-019-0147-3

Four papers report that cancer cells with microsatellite instability, which arises owing to defects in DNA mismatch repair, are selectively vulnerable to knockout of WRN, a RecQ family DNA helicase that could potentially be targeted with small molecules.
Categories: Cancer

Platelets with dangerous cargo

Nature Rev. Cancer - 29 April 2019 - 12:00am

Platelets with dangerous cargo

Platelets with dangerous cargo, Published online: 29 April 2019; doi:10.1038/s41568-019-0146-4

In a study published in Nature Medicine, Malehmir et al. have identified how platelet recruitment contributes to the development of nonalcoholic steatohepatitis and hepatocellular carcinoma in response to high-fat diets in mice.
Categories: Cancer

Cancer overdiagnosis: a biological challenge and clinical dilemma

Nature Rev. Cancer - 25 April 2019 - 12:00am

Cancer overdiagnosis: a biological challenge and clinical dilemma

Cancer overdiagnosis: a biological challenge and clinical dilemma, Published online: 25 April 2019; doi:10.1038/s41568-019-0142-8

The implementation of screening tests for certain cancers has led to the phenomenon of overdiagnosis, whereby a cancer is diagnosed that would otherwise not go on to cause symptoms or death. This Opinion article discusses the effects of overdiagnosis and emerging strategies to reduce overdiagnosis of indolent cancers through an understanding of tumour biology and the tumour microenvironment.
Categories: Cancer

Targeting cancer vulnerabilities with high-dose vitamin C

Nature Rev. Cancer - 9 April 2019 - 12:00am

Targeting cancer vulnerabilities with high-dose vitamin C

Targeting cancer vulnerabilities with high-dose vitamin C, Published online: 09 April 2019; doi:10.1038/s41568-019-0135-7

This Opinion discusses three different mechanisms by which high-dose vitamin C can be selectively toxic to cancer cells. These findings from preclinical studies will be beneficial for the design of clinical trials testing high-dose vitamin C as an anticancer therapy.
Categories: Cancer

Long path to MYC inhibition approaches clinical trials

Nature Rev. Cancer - 9 April 2019 - 12:00am

Long path to MYC inhibition approaches clinical trials

Long path to MYC inhibition approaches clinical trials, Published online: 09 April 2019; doi:10.1038/s41568-019-0141-9

Omomyc, a MYC dominant-negative gene product that is used to inhibit MYC for research purposes, can penetrate cancer cells in vitro and in vivo, bringing it closer to evaluation in the clinic.
Categories: Cancer

Targeting chromatin complexes in fusion protein-driven malignancies

Nature Rev. Cancer - 8 April 2019 - 12:00am

Targeting chromatin complexes in fusion protein-driven malignancies

Targeting chromatin complexes in fusion protein-driven malignancies, Published online: 08 April 2019; doi:10.1038/s41568-019-0132-x

Recurrent oncogenic chromosomal rearrangements frequently involve genes required for chromatin regulation and transcriptional control. This Review discusses mechanistic insights into the chromatin-based functions of many of these oncogenic fusion proteins that are guiding the design of new therapeutic approaches.
Categories: Cancer

Searching for a diagnosis

Nature Rev. Cancer - 5 April 2019 - 12:00am

Searching for a diagnosis

Searching for a diagnosis, Published online: 05 April 2019; doi:10.1038/s41568-019-0140-x

In a study published in Nature Biotechnology, Aalipour et al. have engineered macrophages to create biocompatible diagnostic sensors that can detect tumours as small as 25–50 mm3 in mice, even with co-occurring inflammation.
Categories: Cancer

Targeting cancer cell metabolism in glioblastoma

Nature Rev. Cancer - 3 April 2019 - 12:00am

Targeting cancer cell metabolism in glioblastoma

Targeting cancer cell metabolism in glioblastoma, Published online: 03 April 2019; doi:10.1038/s41568-019-0139-3

Parada and colleagues have identified a novel small-molecule inhibitor of oxidative phosphorylation, which exerts cancer-cell-specific toxicity and inhibits glioblastoma growth in mouse models.
Categories: Cancer

Eliminating protective autophagy in <i>KRAS</i>-mutant cancers

Nature Rev. Cancer - 1 April 2019 - 12:00am

Eliminating protective autophagy in KRAS-mutant cancers

Eliminating protective autophagy in <i>KRAS</i>-mutant cancers, Published online: 01 April 2019; doi:10.1038/s41568-019-0137-5

Two studies show that in the presence of KRAS pathway inhibition, KRAS-mutant pancreatic ductal adenocarcinomas become dependent on autophagy for survival. Removing this protective mechanism through combining MEK or ERK inhibitors with inhibitors of autophagy is likely to be therapeutically beneficial.
Categories: Cancer

What’s driving T cell dysfunction?

Nature Rev. Cancer - 1 April 2019 - 12:00am

What’s driving T cell dysfunction?

What’s driving T cell dysfunction?, Published online: 01 April 2019; doi:10.1038/s41568-019-0138-4

Failure of anticancer immune responses is often due to T cell dysfunction, but the molecular mechanisms underlying this are incompletely understood. Two papers in Nature now identify NR4A transcription factors as key drivers of T cell dysfunction.
Categories: Cancer

Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data

Nature Rev. Cancer - 29 March 2019 - 12:00am

Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data

Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data, Published online: 29 March 2019; doi:10.1038/s41568-019-0133-9

This Opinion, written by many leading experts in small cell lung cancer (SCLC) research, proposes a new model of SCLC subtypes defined by differential expression of four key transcription regulators. Such classification should help to focus and accelerate therapeutic research.
Categories: Cancer

Overflow disrupts the genome

Nature Rev. Cancer - 29 March 2019 - 12:00am

Overflow disrupts the genome

Overflow disrupts the genome, Published online: 29 March 2019; doi:10.1038/s41568-019-0136-6

Hu et al. demonstrate that in pancreatic cells, genomic instability and mutations in KRAS, which drive carcinogenesis, can be promoted by high glucose-induced deregulation of deoxyribonucleotide synthesis.
Categories: Cancer

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