Cancer

Emerging Concepts for Immune Checkpoint Blockade-Based Combination Therapies

Cell Cancer - 9 April 2018 - 12:00am
Checkpoint blockade has formally demonstrated that reactivating anti-tumor immune responses can regress tumors. However, this only occurs in a fraction of patients. Incorporating these therapies in more powerful combinations is thus a logical next step. Here, we review functional roles of immune checkpoints and molecular determinants of checkpoint-blockade clinical activity. Limited-size T cell-infiltrated tumors, differing substantially from “self,” generally respond to checkpoint blockade. Therefore, we propose that reducing tumor burden and increasing tumor immunogenicity are key factors to improve immunotherapy. Lastly, we outline criteria to select proper immunotherapy combination partners and highlight the importance of activity biomarkers for timely treatment optimization.
Categories: Cancer

Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor

Cell Cancer - 9 April 2018 - 12:00am
By analyzing serial biopsies of vincristine-treated canine transmissible venereal tumors, Frampton et al. show that tumor regression occurs in sequential steps involving the activation of the innate immune system and immune infiltration of the tumor, and they identify CCL5 as a possible driver of regression.
Categories: Cancer

Adipocyte p62/SQSTM1 Suppresses Tumorigenesis through Opposite Regulations of Metabolism in Adipose Tissue and Tumor

Cell Cancer - 9 April 2018 - 12:00am
Huang et al. show in a prostate cancer mouse model that p62 loss in adipocytes leads to aggressive disease by increasing osteopontin secretion, which mediates tumor fatty acid oxidation and invasion. P62 deficiency also represses energy-consuming pathways in adipocytes, increasing nutrient availability for tumors.
Categories: Cancer

Too many targets, not enough patients: rethinking neuroblastoma clinical trials

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

Too many targets, not enough patients: rethinking neuroblastoma clinical trials

Too many targets, not enough patients: rethinking neuroblastoma clinical trials, Published online: 09 April 2018; doi:10.1038/s41568-018-0003-x

This Perspective provides an update on targeted therapy development for neuroblastoma and proposes that clinical trial design needs to be rethought in order to provide rigorous, evidence-based assessment of these new therapies in this rare and often deadly paediatric tumour.
Categories: Cancer

Breast cancer: Obesity — tipping the scales of resistance

Nature Rev. Cancer - 6 April 2018 - 12:00am

Breast cancer: Obesity — tipping the scales of resistance

Breast cancer: Obesity — tipping the scales of resistance, Published online: 06 April 2018; doi:10.1038/nrc.2018.31

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.
Categories: Cancer

Mechanisms of cancer resistance in long-lived mammals

Nature Rev. Cancer - 5 April 2018 - 12:00am

Mechanisms of cancer resistance in long-lived mammals

Mechanisms of cancer resistance in long-lived mammals, Published online: 05 April 2018; doi:10.1038/s41568-018-0004-9

In this Opinion article, Seluanov et al. discuss the diverse mechanisms of cancer resistance found in long-lived mammals and argue that studies of unconventional long-lived and cancer-resistant animal species could provide breakthroughs in cancer therapy and prevention.
Categories: Cancer

Breast cancer: External communication

Nature Rev. Cancer - 3 April 2018 - 12:00am

Breast cancer: External communication

Breast cancer: External communication, Published online: 03 April 2018; doi:10.1038/nrc.2018.30

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.
Categories: Cancer

Leukaemia: Powers of prediction

Nature Rev. Cancer - 3 April 2018 - 12:00am

Leukaemia: Powers of prediction

Leukaemia: Powers of prediction, Published online: 03 April 2018; doi:10.1038/nrc.2018.28

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.
Categories: Cancer

Pancreatic cancer: The COMPASS shows the way

Nature Rev. Cancer - 3 April 2018 - 12:00am

Pancreatic cancer: The COMPASS shows the way

Pancreatic cancer: The COMPASS shows the way, Published online: 03 April 2018; doi:10.1038/nrc.2018.29

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

A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers

Cell Cancer - 2 April 2018 - 12:00am
By performing molecular analyses of 2,579 TCGA gynecological (OV, UCEC, CESC, and UCS) and breast tumors, Berger et al. identify five prognostic subtypes using 16 key molecular features and propose a decision tree based on six clinically assessable features that classifies patients into the subtypes.
Categories: Cancer

Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

Cell Cancer - 2 April 2018 - 12:00am
Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1.
Categories: Cancer

Genomic and Functional Approaches to Understanding Cancer Aneuploidy

Cell Cancer - 2 April 2018 - 12:00am
Analyzing >10,000 human cancers, Taylor et al. show that aneuploidy is correlated with somatic mutation rate, expression of proliferation genes, and decreased leukocyte infiltration. Loss of chromosome arm 3p is common in squamous cancers, but deletion of chromosome 3p reduces cell proliferation in vitro.
Categories: Cancer

lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer

Cell Cancer - 2 April 2018 - 12:00am
Wang et al. characterize the epigenetic landscape of lncRNAs genes across a large number of human tumors and cancer cell lines and observe recurrent hypomethylation of lncRNA genes, including EPIC1. EPIC1 RNA promotes cell-cycle progression by interacting with MYC and enhancing its binding to target genes.
Categories: Cancer

Angiogenin/Ribonuclease 5 Is an EGFR Ligand and a Serum Biomarker for Erlotinib Sensitivity in Pancreatic Cancer

Cell Cancer - 29 March 2018 - 12:00am
Wang et al. identify angiogenin (ANG) as a ligand for epidermal growth factor receptor (EGFR). ANG-mediated EGFR activation can trigger oncogenic transformation, and high ANG in the plasma of pancreatic adenocarcinoma patients positively correlates with response to the EGFR inhibitor erlotinib.
Categories: Cancer

GKAP Acts as a Genetic Modulator of NMDAR Signaling to Govern Invasive Tumor Growth

Cell Cancer - 29 March 2018 - 12:00am
Li et al. show that GKAP, a scaffold protein of NMDAR, and its downstream effectors FMRP and HSF1 play important roles in the invasive growth of pancreatic tumors. In several cancer types, low NMDAR activity, based on a transcriptomic signature, associates with favorable patient prognosis.
Categories: Cancer

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies

Cell Cancer - 22 March 2018 - 12:00am
Arce Vargas et al. use a mouse model expressing human FcγRs to show that antibodies with isotypes equivalent to ipilimumab increase the CD8+ to Treg ratio by depleting intra-tumoral Tregs to promote tumor rejection. In melanoma patients, response to ipilimumab is associated with a high affinity FcγR polymorphism.
Categories: Cancer

Complex Interplay between Epitope Specificity and Isotype Dictates the Biological Activity of Anti-human CD40 Antibodies

Cell Cancer - 22 March 2018 - 12:00am
CD40 agonist mAbs are being investigated for cancer treatment, whereas antagonistic mAbs are under investigation for the treatment of autoimmune and inflammatory conditions. Yu et al. show that the activity of a CD40 mAb is determined by an interplay between the location of its epitope within CD40 and its isotype.
Categories: Cancer

Immunosurveillance: Presentation skills

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

Immunosurveillance: Presentation skills

Immunosurveillance: Presentation skills, Published online: 22 March 2018; doi:10.1038/nrc.2018.24

Immunosurveillance: Presentation skills
Categories: Cancer

Immunotherapy: iPSC-based vaccines provoke a response

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

Immunotherapy: iPSC-based vaccines provoke a response

Immunotherapy: iPSC-based vaccines provoke a response, Published online: 22 March 2018; doi:10.1038/nrc.2018.26

Immunotherapy: iPSC-based vaccines provoke a response
Categories: Cancer

Immunotherapy: A therapeutic reservoir

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

Immunotherapy: A therapeutic reservoir

Immunotherapy: A therapeutic reservoir, Published online: 22 March 2018; doi:10.1038/nrc.2018.23

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.
Categories: Cancer

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