52,102 results match your criteria Cancer Res.[Journal]


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

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

HDAC10 Regulates Cancer Stem-like Cell Properties in KRAS-driven Lung Adenocarcinoma.

Cancer Res 2020 Jun 15. Epub 2020 Jun 15.

GW Cancer Center, George Washington University

Activation of oncogenic KRAS is the most common driving event in lung adenocarcinoma development. Despite the existing rationale for targeting activated KRAS and its downstream effectors, the failure of clinical trials to date indicates that the mechanism of KRAS-driven malignancy remains poorly understood. Here we report that histone deacetylase 10 (HDAC10) might function as a putative tumor suppressor in mice carrying a spontaneously activated oncogenic Kras allele. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3613DOI Listing

TAp63-miRNA-AURKA Axis as a Therapeutic Target for Cutaneous Squamous Cell Carcinoma.

Cancer Res 2020 Jun;80(12):2439-2440

Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas.

Despite increasing incidence rates, prognosis of invasive cutaneous squamous cell carcinoma remains poor, mainly due to lack of reliable molecular markers that can be used for targeted therapy. Through genetic and proteogenomic analyses, Davis and colleagues in this issue of define TAp63 and its downstream target miRNAs, miR-30c-2*, and miR-497 as major players that can suppress progression and metastasis of mouse and human cutaneous squamous cell carcinoma. Mimics of miR-30c-2* or miR-497, as well as pharmacologic inhibition of AURKA, a miR-497 target, suppress tumor growth in xenograft mouse models, proposing the TAp63-miR-30c-2*/miR-497-AURKA axis as a potential therapeutic target. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-1215DOI Listing

SKP2 My Lou, My Darling.

Cancer Res 2020 Jun;80(12):2437-2438

Departments of Orthopaedics and Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah.

Myxofibrosarcoma and undifferentiated pleomorphic sarcoma (UPS) lack specific molecular underpinnings, show high rates of metastasis, and display limited responsiveness to current therapies, making them challenging cancers both to treat and to study. It has been noted that MFS and UPS frequently lose function of the tumor suppressor genes and In this issue of , Li and colleagues demonstrate that proliferation in RB1- and TP53-deficient MFS and UPS depends on SKP2; inhibiting SKP2 with the neddylation inhibitor, pevonedistat, halts tumor growth in a panel of patient-derived xenografts. This renders the oncogenic protein SKP2 a promising therapeutic target. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-1046DOI Listing

Chemotherapy-Induced IL8 Upregulates MDR1/ABCB1 in Tumor Blood Vessels and Results in Unfavorable Outcome.

Cancer Res 2020 Jun 14. Epub 2020 Jun 14.

Vascular Biology, Frontier Research Unit, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Tumor endothelial cells (TEC) lining tumor blood vessels actively contribute to tumor progression and metastasis. In addition to tumor cells, TEC may develop drug resistance during cancer treatment, allowing the tumor cells to survive chemotherapy and metastasize. We previously reported that TECs resist paclitaxel treatment via upregulation of ABCB1. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3791DOI Listing

Psychiatric disorders are associated with increased risk of sepsis following a cancer diagnosis.

Cancer Res 2020 Jun 12. Epub 2020 Jun 12.

Department of Medical Epidemiology & Biostatistics, Karolinska Institute

Psychiatric disorders and infections are both common comorbidities among patients with cancer. However, little is known about the role of pre-cancer psychiatric disorders on the subsequent risk of sepsis as a complication of infections among cancer patients. We conducted a cohort study of 362,500 patients with newly diagnosed cancer during 2006-2014 in Sweden. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0502DOI Listing

Engineering the human Fc-region enables direct cell killing by cancer glycan-targeting antibodies without the need for immune effector cells or complement.

Cancer Res 2020 Jun 12. Epub 2020 Jun 12.

Biodiscovery Institute, University of Nottingham

Murine IgG3 glycan-targeting mAb often induces direct cell killing in the absence of immune effector cells or complement via a proinflammatory mechanism resembling oncotic necrosis. This cancer cell killing is due to non-covalent association between Fc regions of neighboring antibodies, resulting in enhanced avidity. Human isotypes do not contain the residues underlying this cooperative binding mode; consequently, the direct cell killing of mouse IgG3 mAb is lost upon chimerization or humanization. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3599DOI Listing

p300-mediated acetylation of histone demethylase JMJD1A prevents its degradation by ubiquitin ligase STUB1 and enhances its activity in prostate cancer.

Cancer Res 2020 Jun 10. Epub 2020 Jun 10.

Biochemistry and Molecular Biology, University of Maryland, Baltimore

The androgen receptor (AR) pathway plays a central role in the development of castration-resistant prostate cancer (CRPC). The histone demethylase JMJD1A has been shown to regulate activities of AR and c-Myc transcription factors and promote prostate cancer progression. Here we report that JMJD1A protein stability is controlled by the ubiquitin ligase STUB1. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0233DOI Listing

A genome-wide pooled shRNA screen identifies PPP2R2A as a predictive biomarker for the response to ATR and CHK1 inhibitors.

Cancer Res 2020 Jun 10. Epub 2020 Jun 10.

Radiation Oncology, The Ohio State University

There is currently a lack of precise predictive biomarkers for patient selection in clinical trials of inhibitors targeting replication stress (RS) response proteins ATR and CHK1. The objective of this study was to identify novel predictive biomarkers for the response to these agents in treating non-small cell lung cancer (NSCLC). A genome-wide loss-of-function screen revealed that tumor suppressor PPP2R2A, a B regulatory subunit of protein phosphatase 2 (PP2A), determines sensitivity to CHK1 inhibition. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0057DOI Listing
June 2020
9.329 Impact Factor

The Lymphatic Cell Environment Promotes Kaposi Sarcoma Development by Prox1-Enhanced Productive Lytic Replication of Kaposi Sarcoma Herpes Virus.

Cancer Res 2020 Jun 9. Epub 2020 Jun 9.

Surgery, University of Southern California

Kaposi's sarcoma (KS) is the most common cancer in HIV-positive individuals and is caused by KS-associated herpesvirus (KSHV). It is believed that a small number of latently infected KS tumor cells undergo spontaneous lytic reactivation to produce viral progeny for infection of new cells. Here we use matched donor-derived human dermal blood and lymphatic endothelial cells (BEC and LEC, respectively) to show that KSHV-infected BEC progressively lose viral genome as they proliferate. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3105DOI Listing
June 2020
9.329 Impact Factor

Oncogenic herpesvirus engages endothelial transcription factors SOX18 and PROX1 to increase viral genome copies and virus production.

Cancer Res 2020 Jun 9. Epub 2020 Jun 9.

Department of Infectious Diseases, Imperial College London

Kaposi sarcoma (KS) is a tumor caused by KS herpesvirus (KSHV) infection and is thought to originate from lymphatic endothelial cells (LEC). While KSHV establishes latency in virtually all susceptible cell types, LEC support spontaneous expression of oncogenic lytic genes, high viral genome copies, and release of infectious virus. It remains unknown the contribution of spontaneous virus production to the expansion of KSHV-infected tumor cells and the cellular factors that render the lymphatic environment unique to KSHV life cycle. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3103DOI Listing
June 2020
9.329 Impact Factor

The EMT transcription factor ZEB2 promotes proliferation of primary and metastatic melanoma while suppressing an invasive, mesenchymal-like phenotype.

Cancer Res 2020 Jun 5. Epub 2020 Jun 5.

Department for Molecular Biomedical Research, CRIG and Ghent University

EMT-inducing transcription factors (TF) are well known for their ability to induce mesenchymal states associated with increased migratory and invasive properties. Unexpectedly, nuclear expression of the EMT-TF ZEB2 in human primary melanoma has been shown to correlate with reduced invasion. We report here that ZEB2 is required for outgrowth for primary melanomas and metastases at secondary sites. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-2373DOI Listing

Moving beyond PARP Inhibition in ATM-Deficient Prostate Cancer.

Cancer Res 2020 Jun;80(11):2085-2086

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

DNA repair defects are found in primary and metastatic prostate cancer. Alterations in the gene are the second most common defect after , but their sensitivity to PARP inhibitors has been questioned by recent clinical literature. The work by Rafiei and colleagues in this issue of now supports this observation with genetically engineered cells and quantitative responses. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0966DOI Listing