52,115 results match your criteria Cancer research[Journal]


Brain Metastasis Cell Lines Panel: a public resource of organotropic cell lines.

Cancer Res 2020 Jul 8. Epub 2020 Jul 8.

Neurology, Neurology Clinic and National Center for Tumor Disease, University Hospital Heidelberg.

Spread of cancer to the brain remains an unmet clinical need in spite of the increasing number of cases among patients with lung, breast cancer and melanoma most notably. Although research on brain metastasis was considered a minor aspect in the past due to its untreatable nature and invariable lethality, nowadays limited but encouraging examples have questioned this statement making it more attractive for basic and clinical researchers. Evidences of its own biological identity (i. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0291DOI Listing

Plasma gelsolin inhibits CD8+ T cell function and regulates glutathione production to confer chemoresistance in ovarian cancer.

Cancer Res 2020 Jul 8. Epub 2020 Jul 8.

Chronic Disease Program, Ottawa Hospital Research Institute

Although initial treatment of ovarian cancer (OVCA) is successful, tumors typically relapse and become resistant to treatment. Due to poor infiltration of effector T cells, patients are mostly unresponsive to immunotherapy. Plasma gelsolin (pGSN) is transported by exosomes (sEV) and plays a key role in OVCA chemoresistance, yet little is known about its role in immunosurveillance. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0788DOI Listing

The pathognomonic FOXL2 C134W mutation alters DNA binding specificity.

Cancer Res 2020 Jul 8. Epub 2020 Jul 8.

Microbiology and Immunology, University of British Columbia

The somatic missense point mutation c.402C>G (p.C134W) in the FOXL2 transcription factor is pathognomonic for adult-type granulosa cell tumors (AGCT) and a diagnostic marker for this tumor type. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0104DOI Listing

Accumulation of molecular aberrations distinctive to hepatocellular carcinoma progression.

Cancer Res 2020 Jul 8. Epub 2020 Jul 8.

Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo.

Cancer develops through the accumulation of genetic and epigenetic aberrations. To identify sequential molecular alterations that occur during the development of hepatocellular carcinoma (HCC), we compared 52 early and 108 overt HCC samples by genome sequencing. Gene mutations in the p53/RB1 pathway, WNT pathway, MLL protein family, SWI/SNF complexes, and AKT/PI3K pathway were common in HCC. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0225DOI Listing

Genome-wide association study data reveal genetic susceptibility to chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma risk.

Cancer Res 2020 Jul 8. Epub 2020 Jul 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute

Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (+/- 500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0447DOI Listing

Mutant FOXL2C134W highjacks SMAD4 and SMAD2/3 to drive adult granulosa cell tumors.

Cancer Res 2020 Jul 8. Epub 2020 Jul 8.

Biotech Research and Innovation Centre (BRIC), The NOVO Nordisk Foundation Centre for Stem Cell Research (Danstem), University of Copenhagen

The mutant protein FOXL2C134W is expressed in at least 95% of adult-type ovarian granulosa cell tumors (AGCT) and is considered to be a driver of oncogenesis in this disease. However, the molecular mechanism by which FOXL2C134W contributes to tumorigenesis is not known. Here we show that mutant FOXL2C134W acquires the ability to bind SMAD4, forming a FOXL2C134W/SMAD4/SMAD2/3 complex that binds a novel hybrid DNA motif AGHCAHAA, unique to the FOXL2C134W mutant. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0259DOI Listing

Leveraging systematic functional analysis to benchmark an in silico framework distinguishes driver from passenger MEK mutants in cancer.

Cancer Res 2020 Jul 8. Epub 2020 Jul 8.

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center

Despite significant advances in cancer precision medicine, a significant hurdle to its broader adoption remains the multitude of variants of unknown significance identified by clinical tumor sequencing and the lack of biologically validated methods to distinguish between functional and benign variants. Here we used functional data on MAP2K1 and MAP2K2 mutations generated in real-time within a co-clinical trial framework to benchmark the predictive value of a three-part in silico methodology. Our computational approach to variant classification incorporated hotspot analysis, three-dimensional molecular dynamics simulation, and sequence paralogy. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0865DOI Listing

Cellular senescence promotes skin carcinogenesis through p38MAPK and p44/p42MAPK signaling.

Cancer Res 2020 Jul 8. Epub 2020 Jul 8.

none, Buck Institute For Research On Aging

Cellular senescence entails an irreversible growth arrest that evolved in part to prevent cancer. Paradoxically, senescent cells secrete pro-inflammatory and growth-stimulatory molecules, termed the senescence-associated secretory phenotype (SASP), which is correlated with cancer cell proliferation in culture and xenograft models. However, at what tumor stage and how senescence and SASP act on endogenous tumor growth in vivo is unknown. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0108DOI Listing

Exosomal noncoding RNAs and tumor drug resistance.

Cancer Res 2020 Jul 8. Epub 2020 Jul 8.

First Affiliated Hospital of Zhengzhou University.

Tumor drug resistance is a major challenge in the treatment of cancer. Non-coding RNAs (ncRNA) play a role in the progression of drug resistance. Recent studies have indicated that exosomes, with their in vitro and in vivo compatibility, are the best natural carrier of ncRNA, and their transport of ncRNA into cells could regulate drug resistance. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0032DOI Listing

Calibration of pathogenicity due to variant-induced leaky splicing defects by using BRCA2 exon 3 as a model system.

Cancer Res 2020 Jul 8. Epub 2020 Jul 8.

Inserm U1245, Normandie Univ, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine

BRCA2 is a clinically actionable gene implicated in breast and ovarian cancer predisposition that has become a high priority target for improving the classification of variants of unknown significance (VUS). Amongst all BRCA2 VUS, those causing partial/leaky splicing defects are the most challenging to classify because the minimal level of full-length transcripts (FL) required for normal function remains to be established. Here, we explored BRCA2 exon 3 (BRCA2e3) as a model for calibrating variant-induced spliceogenicity and estimating thresholds for BRCA2 haploinsufficiency. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0895DOI Listing

Microenvironmental activation of Nrf2 restricts the progression of Nrf2-activated malignant tumors.

Cancer Res 2020 Jul 7. Epub 2020 Jul 7.

Medical Biochemistry, Tohoku University Graduate School of Medicine

The transcription factor Nrf2 activates transcription of cytoprotective genes during oxidative and electrophilic insults. Nrf2 activity is regulated by Keap1 in a stress-dependent manner in normal cells, and somatic loss-of-function mutations of Keap1 are known to induce constitutive Nrf2 activation, especially in lung adenocarcinomas, conferring survival and proliferative benefits to tumors. Therefore, several therapeutic strategies that aim to inhibit Nrf2 in tumors have been developed for the treatment of Nrf2-activated cancers. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-2888DOI Listing

Aquaporin-7 Regulates the Response to Cellular Stress in Breast Cancer.

Cancer Res 2020 Jul 6. Epub 2020 Jul 6.

Chemistry and Biochemistry, Harper Cancer Research Institute, University of Notre Dame

The complex yet interrelated connections between cancer metabolism, gene expression, and oncogenic driver genes have the potential to identify novel biomarkers and drug targets with prognostic and therapeutic value. Here we effectively integrated metabolomics and gene expression data from breast cancer mouse models through a novel unbiased correlation-based network analysis. This approach identified 35 metabolite and 34 gene hubs with the most network correlations. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-2269DOI Listing
July 2020
9.329 Impact Factor

The D2 and D3 sublineages of human papillomavirus 16-positive cervical cancer in Guatemala differ in integration rate and age of diagnosis.

Cancer Res 2020 Jul 6. Epub 2020 Jul 6.

LTG, NIH/NCI/DCEG

Human papillomavirus (HPV) 16 displays substantial sequence variation: four HPV16 lineages (A, B, C, D) have been described as well as multiple sublineages. To identify molecular events associated with HPV16 carcinogenesis, we evaluated viral variation, the integration of HPV16, and somatic mutation in 96 cervical cancer samples from Guatemala. A total of 65% (62/96) of the samples had integrated HPV16 sequences and integration was associated with an earlier age of diagnosis and pre-menopausal disease. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0029DOI Listing

Not Black or White but Shades of Gray: Homologous Recombination Deficiency as a Continuous Variable Modulated by RNF168.

Cancer Res 2020 Jul;80(13):2720-2721

Department of Medicine and Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

In this issue of , the study by Krais and colleagues underscores that DNA damage repair by homologous recombination (HR) is not an all-or-nothing phenomenon, but that HR competency comes on a spectrum, ranging from complete deficiency to proficiency. Residual low-level HR in BRCA1-mutant cancer cells turns out to be critically important for their survival and is afforded by low levels of Histone 2A (H2A) ubiquitination resulting from lowered RNF168 levels. The findings raise the possibility that, if ubiquitination of H2A could be enforced by inhibition of deubiquitinases, residual HR in BRCA1mt cells might be extinguished. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-1248DOI Listing

When the Smoke Clears mA from a Y Chromosome-Linked lncRNA, Men Get an Increased Risk of Cancer.

Cancer Res 2020 Jul;80(13):2718-2719

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.

Long noncoding RNAs (lncRNA) have been implicated in many diseases, including cancer. Although these disease-associated effects have been mostly attributed to the ability of lncRNAs to function as regulatory noncoding transcripts, there is growing evidence that lncRNAs may also encode functional micropeptides. In the current issue of , Wu and colleagues report a micropeptide encoded by a Y chromosome-linked lncRNA that may explain the higher incidence of esophageal cancer in male smokers. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0961DOI Listing

Y Chromosome LncRNA are involved in Radiation Response of Male Non-Small Cell Lung Cancer Cells.

Cancer Res 2020 Jul 2. Epub 2020 Jul 2.

Department of Microbiology, Immunology and Cell Biology, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine

Numerous studies have implicated changes in the Y chromosome in male cancers, yet few have investigated the biological importance of Y chromosome non-coding RNA. Here we identify a group of Y chromosome-expressed long non-coding RNA (lncRNA) that are involved in male non-small cell lung cancer (NSCLC) radiation sensitivity. Radiosensitive male NSCLC cell lines demonstrated a dose-dependent induction of linc-SPRY3-2/3/4 following irradiation, which was not observed in radioresistant male NSCLC cell lines. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-4032DOI Listing

The Fire Within: NF-κB involvement in Non-Small Cell Lung Cancer.

Cancer Res 2020 Jul 2. Epub 2020 Jul 2.

Molecular Oncology Laboratory, Division of Oncology, Department of Medicine, Medical School,University of Patras

Thirty-four years since its discovery, nuclear factor kappa B (NF-κB) remains a transcription factor with great potential for cancer therapy. However, NF-κB-targeted therapies have yet to find a way to be clinically translatable. Here we focus exclusively on the role of NF-κB in non-small cell lung cancer (NSCLC) and discuss its contributing effect on cancer hallmarks such as inflammation, proliferation, survival, apoptosis, angiogenesis, epithelial-mesenchymal transition (EMT), metastasis, stemness, metabolism, and therapy resistance. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3578DOI Listing

FTO-Dependent N6-Methyladenosine Modifications Inhibit Ovarian Cancer Stem Cell Self-Renewal by Blocking cAMP Signaling.

Cancer Res 2020 Jun 30. Epub 2020 Jun 30.

Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University

N6-Methyladenosine (m6A) is the most abundant modification of mammalian messenger RNAs (mRNA). RNA methylation fine tunes RNA stability and translation, altering cell fate. The fat mass- and obesity-associated protein (FTO) is an m6A demethylase with oncogenic properties in leukemia. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-4044DOI Listing

LDtrait: an online tool for identifying published phenotype associations in linkage disequilibrium.

Cancer Res 2020 Jun 30. Epub 2020 Jun 30.

Division of Cancer Epidemiology and Genetics, National Cancer Institute

Genome-wide association studies (GWAS) have identified thousands of germline susceptibility loci associated with risk for cancer as well as a wide range of other traits and diseases. An interest of many investigators is identifying traits or diseases that share common susceptibility loci. We developed LDtrait (https://ldlink. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0985DOI Listing

MR Imaging Distinguishes Tumor Hypoxia Levels of Different Prognostic and Biological Significance in Cervical Cancer.

Cancer Res 2020 Jun 30. Epub 2020 Jun 30.

Department of Radiation Biology, Norwegian Radium Hospital

Tumor hypoxia levels range from mild to severe and have different biological and therapeutical consequences but are not easily assessable in patients. Here we present a method based on diagnostic dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) that reflects a continuous range of hypoxia levels in tumors of cervical cancer patients. Hypoxia images were generated using an established approach based on pixel-wise combination of DCE-MRI parameters Ve and Ktrans, representing oxygen consumption and supply, respectively. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0950DOI Listing

Cancer-associated point mutations in the DLC1 tumor suppressor and other Rho-GAPs occur frequently and are associated with decreased function.

Cancer Res 2020 Jun 30. Epub 2020 Jun 30.

Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute

In advanced cancer, the RHOA GTPase is often active together with reduced expression of genes encoding Rho-specific GTPase-accelerating proteins (Rho-GAP), which negatively regulate RHOA and related GTPases. Here we used the TCGA dataset to examine 12 tumor types (including colon, breast, prostate, pancreas, lung adenocarcinoma and squamous cell carcinoma) for the frequency of codon mutations of 10 Rho-GAP and experimentally tested biochemical and biological consequences for cancer-associated mutants that arose in the DLC1 tumor suppressor gene. DLC1 was the Rho-GAP gene mutated most frequently, with 5-8% of tumors in five of the tumor types evaluated having DLC1 missense mutations. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3984DOI Listing

Traditional Diagnostics versus Disruptive Technology: The role of the pathologist in the era of liquid biopsy.

Cancer Res 2020 Jun 30. Epub 2020 Jun 30.

Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute and Harvard Medical School

Precision medicine in cancer care is predicated on access to several fundamental pieces of data: (1) a precise tumor diagnosis, (2) accurate stage classification, and (3) protein or molecular biomarkers that predict efficacy of targeted therapies. For all cancer patients, these data points are generated by obtaining a tumor sample and subjecting it to analysis by a pathologist and, when appropriate, a molecular pathologist. While tumor diagnosis and pathologic staging (gross and microscopic examination of the primary tumor and draining lymph nodes) require the infrastructure and expertise of an anatomic pathology program, the advent of "liquid biopsy" has driven a shift in molecular biomarker testing away from local pathology labs and into high-throughput, centralized (and often for-profit) laboratories. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0134DOI Listing

CXCR4 in tumor epithelial cells mediates desmoplastic reaction in pancreatic ductal adenocarcinoma.

Cancer Res 2020 Jun 30. Epub 2020 Jun 30.

Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University.

Pancreatic ductal adenocarcinoma (PDAC) features abundant stromal cells with an excessive extracellular matrix (ECM), termed the desmoplastic reaction. CXCR4 is a cytokine receptor for stromal cell-derived factor-1 (CXCL12) expressed in PDAC, but its roles in PDAC and the characteristic desmoplastic reaction remain unclear. Here we generated a mouse model of PDAC with conditional knockout of Cxcr4 (KPC-Cxcr4-KO) by crossing Cxcr4 flox mice with Pdx1-Cre;KrasLSL-G12D/+;Trp53LSL-R172H/+ (KPC-Cxcr4-WT) mice to assess the development of pancreatic intraepithelial neoplasia (PanIN) and pancreatic cancers. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-2745DOI Listing

Obesity/type 2 diabetes-associated liver tumors are sensitive to Cyclin D1 deficiency.

Cancer Res 2020 Jun 30. Epub 2020 Jun 30.

Cancer Biology, Dana-Farber Cancer Institute

Type 2 diabetes, which is mainly linked to obesity, is associated with increased incidence of liver cancer. We have previously found that in various models of obesity/diabetes, hyperinsulinemia maintains heightened hepatic expression of Cyclin D1, suggesting a plausible mechanism linking diabetes and liver cancer progression. Here we show that Cyclin D1 is greatly elevated in human livers with diabetes and is among the most significantly upregulated genes in obese/diabetic liver tumors. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0106DOI Listing

KRASQ61H preferentially signals through MAPK in a RAF dimer-dependent manner in non-small cell lung cancer.

Cancer Res 2020 Jun 30. Epub 2020 Jun 30.

Departments of Biochemistry and Radiation Oncology, The University of Texas Southwestern Medical Center at Dallas

Assembly of RAS molecules into complexes at the cell membrane is critical for RAS signaling. We previously showed that oncogenic KRAS codon 61 mutations increase its affinity for RAF, raising the possibility that KRASQ61H, the most common KRAS mutation at codon 61, upregulates RAS signaling through mechanisms at the level of RAS assemblies. We show here that KRASQ61H exhibits preferential binding to RAF relative to PI3K in cells, leading to enhanced MAPK signaling in in vitro models and human NSCLC tumors. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0448DOI Listing

HDAC6 plays a non-canonical role in the regulation of anti-tumor immune responses, dissemination, and invasiveness of breast cancer.

Cancer Res 2020 Jun 30. Epub 2020 Jun 30.

Biochemistry and Molecular Medicine, George Washington University

Despite the outstanding clinical results of immune checkpoint blockade (ICB) in melanoma and other cancers, clinical trials in breast cancer have reported low responses to these therapies. Current efforts are now focused on improving the treatment efficacy of ICB in breast cancer using new combination designs such as molecularly targeted agents, including histone deacetylase inhibitors (HDACi). These epigenetic drugs have been widely described as potent cytotoxic agents for cancer cells. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3738DOI Listing

Lymphatic vessels in tumor dissemination vs. immunotherapy.

Cancer Res 2020 Jun 30. Epub 2020 Jun 30.

Translational Cancer Medicine Program, Biomedicum Helsinki, University of Helsinki

During the growth of various cancers, primary tumors can escape anti-tumor immune responses of their host and eventually disseminate into distant organs. Peritumoral lymphatic vessels connect the primary tumor to lymph nodes, facilitating tumor entry into lymph nodes, systemic circulation, and metastasis. Lymph node metastases that occur frequently provide sites of tumor cell spread, whereas tumor antigen transfer into and presentation in tumor-draining lymph nodes induce activation of tumor-specific T-lymphocyte responses that can result in cytolytic targeting of the tumor. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0156DOI Listing

Palmitoylated proteins on AML-derived extracellular vesicles promote myeloid-derived suppressor cell differentiation via TLR2/Akt/mTOR signaling.

Cancer Res 2020 Jun 30. Epub 2020 Jun 30.

Department of Internal Medicine 5 Hematology and Oncology, University of Erlangen

Acute myeloid leukemia (AML) represents the most common acute leukemia amongst adults. Despite recent progress in diagnosis and treatment, long-term outcome remains unsatisfactory. The success of allogeneic stem cell transplantation underscores the immunoresponsive nature of AML creating the basis for further exploiting immunotherapies. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0024DOI Listing

Extracellular vesicles from cancer-associated fibroblasts containing annexin A6 induces FAK-YAP activation by stabilizing β1 integrin, enhancing drug resistance.

Cancer Res 2020 Jun 30. Epub 2020 Jun 30.

Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University

Extracellular vesicles (EV) from cancer-associated fibroblasts (CAF) are composed of diverse payloads. Although CAF impact the aggressive characteristics of gastric cancer (GC) cells, the contribution of CAF-EV to GC progression has not been elucidated. Here we investigated the molecular mechanism of the changes in GC characteristics induced by CAF-EV. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3803DOI Listing

Noninvasive MRI native T1 mapping detects response to MYCN-targeted therapies in the Th-MYCN model of neuroblastoma.

Cancer Res 2020 Jun 28. Epub 2020 Jun 28.

Division of Radiotherapy and Imaging, The Institute of Cancer Research, London

Noninvasive early indicators of treatment response are crucial to the successful delivery of precision medicine in children with cancer. Neuroblastoma is a common solid tumor of young children that arises from anomalies in neural crest development. Therapeutic approaches aiming to destabilize MYCN protein, such as small molecule inhibitors of Aurora A and mTOR, are currently being evaluated in early phase clinical trials in children with high-risk MYCN-driven disease, with limited ability to evaluate conventional pharmacodynamic biomarkers of response. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0133DOI Listing

YAP Enhances Tumor Cell Dissemination by Promoting Intravascular Motility and Re-entry into Systemic Circulation.

Cancer Res 2020 Jun 26. Epub 2020 Jun 26.

David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology

The oncogene YAP has been shown previously to promote tumor growth and metastasis. However, how YAP influences the behavior of tumor cells traveling within the circulatory system has not been as well explored. Given that rate-limiting steps of metastasis are known to occur while tumor cells enter, travel through, or exit circulation, we sought to study how YAP influences tumor cell behavior within the circulatory system. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0212DOI Listing

Interaction with CD68 and regulation of GAS6 expression by endosialin in fibroblasts drives recruitment and polarization of macrophages in hepatocellular carcinoma.

Cancer Res 2020 Jun 26. Epub 2020 Jun 26.

State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University

Fibroblasts and macrophages play key roles in the development of hepatocellular carcinoma (HCC). However, crosstalk between these two kinds of cells has not been well-studied. Endosialin (CD248/TEM1) is a transmembrane glycoprotein that is expressed in certain cancer cells, tumor stromal cells, and pericytes. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-2691DOI Listing
June 2020
9.329 Impact Factor

Rb and p53 execute distinct roles in the development of pancreatic neuroendocrine tumors.

Cancer Res 2020 Jun 26. Epub 2020 Jun 26.

Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University.

Pancreatic neuroendocrine tumors (PanNET) were classified into grades (G) 1-3 by the World Health Organization in 2017, but the precise mechanisms of PanNET initiation and progression have remained unclear. In this study, we used a genetically engineered mouse model to investigate the mechanisms of PanNET formation. Although pancreas-specific deletion of the Rb gene (Pdx1-Cre;Rbf/f) in mice did not affect pancreatic exocrine cells, the α-cell/β-cell ratio of islet cells was decreased at 8 months of age. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-2232DOI Listing

A Pygopus 2-histone interaction is critical for cancer cell de-differentiation and progression in malignant breast cancer.

Cancer Res 2020 Jun 25. Epub 2020 Jun 25.

Department of Biomedicine, University of Basel

Pygopus 2 (Pygo2) is a co-activator of Wnt/β-catenin signaling that can bind bi- or trimethylated lysine 4 of histone-3 (H3K4me2/3) and participate in chromatin reading and writing. It remains unknown whether the Pygo2- H3K4me2/3 association has a functional relevance in breast cancer progression in vivo. To investigate the functional relevance of histone binding activity of Pygo2 in malignant progression of breast cancer, we generated a knock-in mouse model where binding of Pygo2 to H3K4me2/3 was rendered ineffective. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-2910DOI Listing

NRAS status determines sensitivity to SHP2 inhibitor combination therapies targeting the RAS-MAPK pathway in neuroblastoma.

Cancer Res 2020 Jun 25. Epub 2020 Jun 25.

Cell Biology Program, Hospital for Sick Children

Survival for high-risk neuroblastoma (NB) remains poor and treatment for relapsed disease rarely leads to long-term cures. Large sequencing studies of NB tumors from diagnosis have not identified common targetable driver mutations other than the 10% of tumors that harbor mutations in the anaplastic lymphoma kinase (ALK) gene. However, at NB recurrence, more frequent mutations in genes in the RAS-MAPK pathway have been detected. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3822DOI Listing

Platelet-specific PDGFB ablation impairs tumor vessel integrity and promotes metastasis.

Cancer Res 2020 Jun 25. Epub 2020 Jun 25.

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center

Platelet-derived growth factor B (PDGFB) plays a crucial role in recruitment of PDGF receptor beta (PDGFRbeta)-positive pericytes to blood vessels. The endothelium is an essential source of PDGFB in this process. Platelets constitute a major reservoir of PDGFB and are continuously activated in the tumor microenvironment, exposing tumors to the plethora of growth factors contained in platelet granules. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3533DOI Listing

FIP200 suppresses immune checkpoint therapy responses in breast cancers by limiting AZI2/TBK1/IRF signaling independent of its canonical autophagy function.

Cancer Res 2020 Jun 24. Epub 2020 Jun 24.

Cancer Biology, University of Cincinnati College of Medicine

Immune checkpoint inhibitors (ICI) have the potential to induce durable therapeutic responses, yet response rates in breast cancer are modest and limited to particular subtypes. To expand the applicability of ICI, we examined the role of an essential autophagy gene, FIP200, which has been shown to be important for tumor progression in mammary tumors. Specific disruption of the autophagy function of FIP200 or complete ablation of FIP200 in genetic mouse models revealed that FIP200 autophagy function was required for progression of PyMT-driven mammary tumors. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0519DOI Listing
June 2020
9.329 Impact Factor

p38gamma MAPK is essential for aerobic glycolysis and pancreatic tumorigenesis.

Cancer Res 2020 Jun 24. Epub 2020 Jun 24.

Department of Pharmacology and Toxicology, Medical College of Wisconsin

KRAS is mutated in most pancreatic ductal adenocarcinomas (PDAC) and yet remains undruggable. Here we report that p38gamma MAPK, which promotes PDAC tumorigenesis by linking KRAS signaling and aerobic glycolysis (also called the Warburg effect), is a novel therapeutic target. p38gamma interacted with a glycolytic activator PFKFB3 that was dependent on mutated KRAS. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3281DOI Listing

Deletion of Glutathione S-Transferase Omega 1 Activates Type I Interferon Genes and Downregulates Tissue Factor.

Cancer Res 2020 Jun 22. Epub 2020 Jun 22.

Medicinal Chemistry, University of Michigan-Ann Arbor

Glutathione S-transferase omega 1 (GSTO1) is an atypical GST isoform that is overexpressed in several cancers and has been implicated in drug resistance. Currently, no small-molecule drug targeting GSTO1 is under clinical development. Here we have validated GSTO1 as an impactful target in oncology. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0530DOI Listing

Circulating proteoglycan endocan mediates EGFR-driven progression of non-small cell lung cancer.

Cancer Res 2020 Jun 19. Epub 2020 Jun 19.

Graduate Institute of Clinical Medicine, Taipei Medical University.

Although new generations of EGFR-tyrosine kinase inhibitors (EGFR-TKI) have been developed for the treatment of non-small cell lung cancer (NSCLC) patients with EGFR-mutant tumors, TKI resistance often returns as a result of additional EGFR mutations. In addition to seeking for next generation EGFR-TKI, developing novel EGFR-targeting strategies may hold the key to overcome the vicious cycle of TKI resistance. Endocan is known as a receptor tyrosine kinase ligand enhancer in tumorigenesis, but the impact of endocan on EGFR-driven NSCLC progression remains unknown. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0005DOI Listing

Pharmacokinetic profiles determine optimal combination treatment schedules in computational models of drug resistance.

Cancer Res 2020 Jun 19. Epub 2020 Jun 19.

Department of Data Sciences, Dana-Farber Cancer Institute

Identification of optimal schedules for combination drug administration relies on accurately estimating the correct pharmacokinetics, pharmacodynamics, and drug interaction effects. Misspecification of pharmacokinetics can lead to wrongly predicted timing or order of treatments, leading to schedules recommended based on incorrect assumptions about absorption and elimination of a drug and its effect on tumor growth. Here we developed a computational modeling platform and software package for combination treatment strategies with flexible pharmacokinetic profiles and multidrug interaction curves that are estimated from data. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0056DOI Listing

IL-6 fuels durable memory for Th17 cell-mediated responses to tumors.

Cancer Res 2020 Jun 19. Epub 2020 Jun 19.

Hollings Cancer Center, Medical University of South Carolina.

The accessibility of adoptive T cell transfer therapies (ACT) is hindered by cost and time required for product development. Here we describe a streamlined ACT protocol using Th17 cells expanded only four days ex vivo. While shortening expansion compromised cell yield, this method licensed Th17 cells to eradicate large tumors to a greater extent than cells expanded longer term. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3685DOI Listing

Extracellular-regulated protein kinase 5-mediated control of p21 expression promotes macrophage proliferation associated with tumor growth and metastasis.

Cancer Res 2020 Jun 19. Epub 2020 Jun 19.

Faculty of Life Sciences, University of Manchester

The presence of immunosuppressive macrophages that become activated in the tumor microenvironment constitutes a major factor responsible for tumor growth and malignancy. In line with this knowledge, we report here that macrophage proliferation is a significant feature of advanced stages of cancer. Moreover, we have found that a high proportion of proliferating macrophages in human tumors express extracellular-regulated protein kinase 5 (ERK5). Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-2416DOI Listing

ATF3 coordinates anti-tumor synergy between epigenetic drugs and protein disulfide isomerase inhibitors.

Cancer Res 2020 Jun 19. Epub 2020 Jun 19.

Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina

Histone deacetylase inhibitors (HDACi) are largely ineffective in the treatment of solid tumors. In this study, we describe a new class of protein disulfide isomerase (PDI) inhibitors that significantly and synergistically enhance the anti-tumor activity of HDACi in glioblastoma and pancreatic cancer preclinical models. RNA-seq screening coupled with gene silencing studies identified ATF3 as the driver of this anti-tumor synergy. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-4046DOI Listing

Autocrine IL6-mediated activation of the STAT3-DNMT axis silences the TNFα-RIP1 necroptosis pathway to sustain survival and accumulation of myeloid-derived suppressor cells.

Cancer Res 2020 Jun 17. Epub 2020 Jun 17.

Dept. of Biochemistry and Molecular Biology, Medical College of Georgia

Although accumulation of myeloid-derived suppressor cells (MDSC) is a hallmark of cancer, the underlying mechanism of this accumulation within the tumor microenvironment remains incompletely understood. We report here that TNFα-RIP1-mediated necroptosis regulates accumulation of MDSCs. In tumor-bearing mice, pharmacological inhibition of DNMT with the DNA methyltransferease inhibitor decitabine (DAC) decreased MDSC accumulation and increased activation of antigen-specific cytotoxic T lymphocytes (CTL). Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3670DOI Listing

Oncogene-induced senescence limits the progression of pancreatic neoplasia through production of Activin A.

Cancer Res 2020 Jun 17. Epub 2020 Jun 17.

Tumoral Escape/team4, INSERM U1052/CNRS UMR5286/Univ. Lyon1 - Cancer Research Center Lyon (CRCL)

Pancreatic ductal adenocarcinoma (PDA) is a deadly and aggressive cancer. Understanding mechanisms that drive pre-neoplastic pancreatic lesions is necessary to improve early diagnostic and therapeutic strategies. Mutations and inactivation of activin-like kinase (ALK4) have been demonstrated to favor PDA onset. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3763DOI Listing

A novel locus predicts spermatogenic recovery among childhood cancer survivors exposed to alkylating agents.

Cancer Res 2020 Jun 17. Epub 2020 Jun 17.

Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital.

Exposure to high doses of alkylating agents is associated with increased risk of impaired spermatogenesis among non-irradiated male survivors of childhood cancer, but there is substantial variation in this risk. Here we conducted a genetic study for impaired spermatogenesis utilizing whole genome sequencing data from 167 non-irradiated male childhood cancer survivors of European ancestry from the St. Jude Lifetime Cohort treated with cyclophosphamide equivalent dose (CED)≥4000 mg/m2. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0093DOI Listing

How Tumor Cell Dedifferentiation Drives Immune Evasion And Resistance to Immunotherapy.

Cancer Res 2020 Jun 18. Epub 2020 Jun 18.

Department of Medicine, Perelman School of Medicine, University of Pennsylvania

Immunotherapy has revolutionized cancer treatment, yet most patients do not respond. While tumor antigens are needed for effective immunotherapy, a favorable tumor immune microenvironment is also critical. In this review, we discuss emerging evidence that tumor cells exploit cellular plasticity and dedifferentiation programs to avoid immune surveillance, which in turn drives metastatic dissemination and resistance to immunotherapy. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-1420DOI Listing

Oxygen-enhanced optoacoustic tomography reveals the effectiveness of targeting heme and oxidative phosphorylation at normalizing tumor vascular oxygenation.

Cancer Res 2020 Jun 16. Epub 2020 Jun 16.

Department of Radiology, The University of Texas Southwestern Medical Center

Multispectral optoacoustic tomography (MSOT) is an emerging noninvasive imaging modality that can detect real-time dynamic information about the tumor microenvironment (TME) in humans and animals. Oxygen enhanced (OE)-MSOT can monitor tumor vasculature and oxygenation during disease development or therapy. Here we used MSOT and OE-MSOT to examine in mice the response of human non-small cell lung cancer (NSCLC) xenografts to a new class of anti-tumor drugs, heme-targeting agents heme-sequestering peptide 2 (HSP2) and cyclopamine tartrate (CycT). Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3247DOI Listing

Comprehensive analysis of radiomic datasets by RadAR.

Cancer Res 2020 Jun 15. Epub 2020 Jun 15.

Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence.

Quantitative analysis of biomedical images, referred to as radiomics, is emerging as a promising approach to facilitate clinical decisions and improve patient stratification. The typical radiomic workflow includes image acquisition, segmentation, feature extraction, and analysis of high-dimensional datasets. While procedures for primary radiomic analyses have been established in recent years, processing the resulting radiomic datasets remains a challenge due to the lack of specific tools for doing so. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0332DOI Listing