Cancer

Metastasis: Go with the flow

Nature Rev. Cancer - 22 March 2018 - 12:00am

Metastasis: Go with the flow

Metastasis: Go with the flow, Published online: 22 March 2018; doi:10.1038/nrc.2018.25

Metastasis: Go with the flow
Categories: Cancer

Targeted therapy: Tipping the splicing balance to kill cancer cells

Nature Rev. Cancer - 22 March 2018 - 12:00am

Targeted therapy: Tipping the splicing balance to kill cancer cells

Targeted therapy: Tipping the splicing balance to kill cancer cells, Published online: 22 March 2018; doi:10.1038/nrc.2018.27

A paper in Nature Medicine describes a novel, orally available splicing modulator that preferentially kills cancer cells with mutations in splicing factors in culture and in mouse models.
Categories: Cancer

Cell motility in cancer invasion and metastasis: insights from simple model organisms

Nature Rev. Cancer - 16 March 2018 - 12:00am

Cell motility in cancer invasion and metastasis: insights from simple model organisms

Cell motility in cancer invasion and metastasis: insights from simple model organisms, Published online: 16 March 2018; doi:10.1038/nrc.2018.15

In this Review, Stuelten et al. outline insights with relevance to human cancer invasion and metastasis that have come from the study of cell motility in non-mammalian model organisms.
Categories: Cancer

Dysregulated IL-18 Is a Key Driver of Immunosuppression and a Possible Therapeutic Target in the Multiple Myeloma Microenvironment

Cell Cancer - 15 March 2018 - 12:00am
Nakamura et al. show that IL-18 produced by the multiple myeloma (MM) niche promotes MM progression in a CD8+ T cell-dependent manner in a mouse model and that IL-18 could be a potential therapeutic target in MM. High levels of bone marrow plasma IL-18 are associated with poor overall survival in MM patients.
Categories: Cancer

Targeting mRNA Decapping in AML

Cell Cancer - 12 March 2018 - 12:00am
In this issue of Cancer Cell, Yamauchi et al. identify a dependency of acute myeloid leukemia (AML) on DCPS, which catalyzes the final step of 3′-to-5′ mRNA decay and is implicated in numerous aspects of RNA metabolism. DCPS is targetable with a clinical inhibitor, underscoring the translational importance of this discovery.
Categories: Cancer

ORY-1001: Overcoming the Differentiation Block in AML

Cell Cancer - 12 March 2018 - 12:00am
In this issue of Cancer Cell, Maes and colleagues report in vitro and in vivo findings with ORY-1001—an oral, highly potent and selective covalent small-molecule inhibitor of lysine-specific demethylase 1 (LSD1)—in development for acute myeloid leukemia (AML), as well as correlative data from two AML patients receiving ORY-1001.
Categories: Cancer

A Non-canonical Polycomb Dependency in Synovial Sarcoma

Cell Cancer - 12 March 2018 - 12:00am
Disruptions in the antagonistic balance between the chromatin-modifying Polycomb and Trithorax group proteins drive many malignancies. In this issue of Cancer Cell, Banito et al. describe how the SS18-SSX oncogenic fusion protein in synovial sarcoma directly co-opts these complexes to drive gene dysregulation and sustain the transformed state.
Categories: Cancer

Glucose Metabolism in Cancer: The Saga of Pyruvate Kinase Continues

Cell Cancer - 12 March 2018 - 12:00am
Altered glucose metabolism is common in cancer. In this issue of Cancer Cell, Morita et al. report new mouse models that express specific isoforms of pyruvate kinase to study glycolysis in tumors. They report several unanticipated findings that challenge current ideas in cancer metabolism.
Categories: Cancer

NRL and CRX Define Photoreceptor Identity and Reveal Subgroup-Specific Dependencies in Medulloblastoma

Cell Cancer - 12 March 2018 - 12:00am
Garancher et al. show that NRL and CRX are master transcriptional regulators of a photoreceptor-specific differentiation program critical for group 3 medulloblastoma (MB) maintenance. They identify BCL-XL as a key NRL target and provide evidence supporting anti-BCL therapy as a strategy for some MB patients.
Categories: Cancer

Tumor-Repopulating Cells Induce PD-1 Expression in CD8+ T Cells by Transferring Kynurenine and AhR Activation

Cell Cancer - 12 March 2018 - 12:00am
Liu et al. find that tumor-repopulating cells (TRCs) regulate PD-1 expression in CD8+ T cells. TRCs secrete kynurenine that is taken up by T cells and activates AhR, which directly regulates PD-1 expression. Blockade of this pathway enhances adoptive T cell therapy efficacy in a mouse melanoma model.
Categories: Cancer

PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth

Cell Cancer - 12 March 2018 - 12:00am
The relative importance of PKM isoforms in tumor growth has been controversial. Morita et al. show that PKM1 promotes the growth of multiple tumor models using mouse lines expressing PKM1 or PKM2 from the endogenous Pkm locus. PKM1 is expressed in human SCLC, and it is important for SCLC cell proliferation.
Categories: Cancer

Loss of KDM6A Activates Super-Enhancers to Induce Gender-Specific Squamous-like Pancreatic Cancer and Confers Sensitivity to BET Inhibitors

Cell Cancer - 12 March 2018 - 12:00am
Andricovich et al. show that KDM6A loss, via aberrant activation of super-enhancers regulating several oncogenes, induces squamous-like, metastatic pancreatic cancer in females. In males, both KDM6A and UTY loss is required to induce squamous-like tumors. Importantly, KDM6A-deficient pancreatic cancer is sensitive to BET inhibitors.
Categories: Cancer

Unique Metabolic Adaptations Dictate Distal Organ-Specific Metastatic Colonization

Cell Cancer - 12 March 2018 - 12:00am
Metastases arising from tumors have the proclivity to colonize specific organs, suggesting that they must rewire their biology to meet the demands of the organ colonized, thus altering their primary properties. Each metastatic site presents distinct metabolic challenges to a colonizing cancer cell, ranging from fuel and oxygen availability to oxidative stress. Here, we discuss the organ-specific metabolic adaptations that cancer cells must undergo, which provide the ability to overcome the unique barriers to colonization in foreign tissues and establish the metastatic tissue tropism phenotype.
Categories: Cancer

Systematic Functional Annotation of Somatic Mutations in Cancer

Cell Cancer - 12 March 2018 - 12:00am
Ng et al. develop a moderate-throughput functional genomic platform and use it to annotate >1,000 cancer variants of unknown significance. The approach is sufficiently sensitive to identify weak drivers, potentially doubling the number of driver mutations characterized in clinically actionable genes.
Categories: Cancer

Sense-Antisense lncRNA Pair Encoded by Locus 6p22.3 Determines Neuroblastoma Susceptibility via the USP36-CHD7-SOX9 Regulatory Axis

Cell Cancer - 12 March 2018 - 12:00am
Mondal et al. show a sense/antisense lncRNA pair expressed from the neuroblastoma (NB) risk-associated 6p22.3 locus is important for retinoic acid-induced NB differentiation gene-regulatory network by controlling CHD7 stability via modulating the cellular localization of the ubiquitin specific protease USP36.
Categories: Cancer

BRD4 Inhibition Is Synthetic Lethal with PARP Inhibitors through the Induction of Homologous Recombination Deficiency

Cell Cancer - 12 March 2018 - 12:00am
Sun et al. show that inhibition of BRD4 induces homologous recombination deficiency, through depletion of CtBP, in cells across multiple tumor types and sensitizes them to PARP inhibition. Thus, inhibition of BRD4 reverses resistance to PARP inhibitors and expands the potential use of PARP inhibitors.
Categories: Cancer

Non-angiogenic tumours and their influence on cancer biology

Nature Rev. Cancer - 9 March 2018 - 12:00am

Non-angiogenic tumours and their influence on cancer biology

Non-angiogenic tumours and their influence on cancer biology, Published online: 09 March 2018; doi:10.1038/nrc.2018.14

In this Opinion article, Donnem et al. outline the evidence for non-angiogenic tumours, which use pre-existing blood vessels to support tumour growth, and discuss the studies that are beginning to define their unique biology.
Categories: Cancer

Immunotherapy: Tear down this wall

Nature Rev. Cancer - 9 March 2018 - 12:00am

Immunotherapy: Tear down this wall

Immunotherapy: Tear down this wall, Published online: 09 March 2018; doi:10.1038/nrc.2018.22

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.
Categories: Cancer

Epigenetics: Methylating patterns

Nature Rev. Cancer - 9 March 2018 - 12:00am

Epigenetics: Methylating patterns

Epigenetics: Methylating patterns, Published online: 09 March 2018; doi:10.1038/nrc.2018.21

Xie et 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.
Categories: Cancer

Metastasis: Staying organized

Nature Rev. Cancer - 2 March 2018 - 12:00am

Metastasis: Staying organized

Metastasis: Staying organized, Published online: 02 March 2018; doi:10.1038/nrc.2018.20

A recent study published in Nature Cell Biology has shown that tumour spheres that maintain an inverted epithelial architecture originate from primary colorectal cancers and can collectively invade the peritoneum, initiating metastasis.
Categories: Cancer

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