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Peritumoral Venous Vessels: Autobahn and Portal for T cells to Melanoma Brain Metastasis Cancer Res. (IF 12.5) Pub Date : 2024-11-08 Benjamin Izar, Minah Kim
Melanoma brain metastasis is associated with high morbidity and mortality and remains a major clinical challenge. Despite recent successes with combination immune checkpoint inhibitors (ICI) in the treatment of affected patients, the mechanistic underpinnings of T cell entry and response to these drugs in brain metastasis are poorly understood. Using real-time intravital microscopy, Messmer and colleagues
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Fluorescence Lifetime Imaging Enables In vivo Quantification of PD-L1 Expression and Inter-tumoral Heterogeneity Cancer Res. (IF 12.5) Pub Date : 2024-11-08 Rahul Pal, Murali Krishnamoorthy, Aya Matsui, Homan Kang, Satoru Morita, Hajime Taniguchi, Tatsuya Kobayashi, Atsuyo Morita, Hak Soo Choi, Dan G. Duda, Anand T.N. Kumar
Patient selection for cancer immunotherapy requires precise, quantitative readouts of biomarker expression in intact tumors that can be reliably compared across multiple subjects over time. The current clinical standard biomarker for assessing immunotherapy response is programmed death-ligand-1 (PD-L1) expression, typically quantified using immunohistochemistry. This method, however, only provides
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Modeling Drug Responses and Evolutionary Dynamics using Patient-Derived Xenografts Reveals Precision Medicine Strategies for Triple Negative Breast Cancer Cancer Res. (IF 12.5) Pub Date : 2024-11-08 Abigail Shea, Yaniv Eyal-Lubling, Daniel Guerrero-Romero, Raquel Manzano Garcia, Wendy Greenwood, Martin O’Reilly, Dimitra Georgopoulou, Maurizio Callari, Giulia Lerda, Sophia Wix, Agnese Giovannetti, Riccardo Masina, Elham Esmaeilishirazifard, Wei Cope, Alistair G. Martin, Ai Nagano, Lisa Young, Steven Kupczak, Yi Cheng, Helen Bardwell, Elena Provenzano, Justine Kane, Jonny Lay, Louise Grybowicz,
The inter- and intra-tumor heterogeneity of triple negative breast cancers (TNBC), which is reflected in diverse drug responses, interplays with tumor evolution. Here, we developed a preclinical experimental and analytical framework using treatment-naive TNBC patient-derived tumor xenografts (PDTX) to test their predictive value in personalized cancer treatment approaches. Patients and their matched
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Loss of CDKN2A Enhances the Efficacy of Immunotherapy in EGFR Mutant Non-Small Cell Lung Cancer Cancer Res. (IF 12.5) Pub Date : 2024-11-08 Simeng Wang, Jia-Cheng Lai, Yu Li, Chengfang Tang, Jiajia Lu, Min Han, Xianjiang Ye, Lina Jia, Wei Cui, Jingyu Yang, Chunfu Wu, Lihui Wang
Mutant epidermal growth factor receptor (EGFR) is a common driver of non-small cell lung cancer (NSCLC). While mutant EGFR has been reported to limit the efficacy of immunotherapy, a subset of EGFR mutant NSCLC patients benefit from treatment with immune checkpoint inhibitors. A better understanding of how co-occurring genomic alterations in oncogenic driver genes impact immunotherapy efficacy may
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CSTF2 Supports Hypoxia Tolerance in Hepatocellular Carcinoma by Enabling m6A Modification Evasion of PGK1 to Enhance Glycolysis Cancer Res. (IF 12.5) Pub Date : 2024-11-08 Qiangnu Zhang, Yusen Zhang, Chuli Fu, Xiaoyan He, Zuotian Huang, Geyan Wu, Teng Wei, Wen Jin, Lesen Yan, Meilong Wu, Gongze Peng, LinLan Fan, Mingyue Li, Yuehua Guo, Jiangang Bi, Yu Bai, Stephanie Roessler, Guang-Rong Yan, Liping Liu
Cleavage stimulation factor subunit 2 (CSTF2) is a fundamental factor in the regulation of 3'-end cleavage and alternative polyadenylation of pre-mRNAs. Previous work has identified a tumor-promoting role of CSTF2, suggesting that it may represent a potential therapeutic target. Here, we aimed to elucidate the mechanistic function of CSTF2 in hepatocellular carcinoma (HCC). CSTF2 upregulation was frequent
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Spatial and Single Cell Analyses Reveal Heterogeneity of DNAM-1 Receptor-Ligand Interactions that Instructs Intratumoral γδT-Cell Activity Cancer Res. (IF 12.5) Pub Date : 2024-11-08 Xiaolin Wang, Hui Wang, Zhengjing Lu, Xiangjun Liu, Wenjia Chai, Wei Wang, Jun Feng, Shen Yang, Wei Yang, Haiyan Cheng, Chenghao Chen, Shihan Zhang, Nian Sun, Qiaoyin Liu, Qiliang Li, Wenqi Song, Fang Jin, Qi Zeng, Shengcai Wang, Yan Su, Huanmin Wang, Xin Ni, Jingang Gui
The dynamic interplay between tumor cells and γδT cells within the tumor microenvironment (TME) significantly influences disease progression and immunotherapy outcome. Here, we delved into the modulation of γδT-cell activation by tumor cell ligands CD112 and CD155, which interact with the activating receptor DNAM-1 on γδT cells. Spatial and single cell RNA sequencing (scRNA-seq), as well as spatial
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PHGDH Induction by MAPK is Essential for Melanoma Formation and Creates an Actionable Metabolic Vulnerability Cancer Res. (IF 12.5) Pub Date : 2024-11-04 Neel Jasani, Xiaonan Xu, Benjamin Posorske, Yumi Kim, Kaizhen Wang, Olga Vera, Kenneth Y. Tsai, Gina M. DeNicola, Florian A. Karreth
Overexpression of PHGDH, the rate-limiting enzyme in the serine synthesis pathway, promotes melanomagenesis, melanoma cell proliferation, and survival of metastases in serine-low environments such as the brain. Here, we found that PHGDH is universally increased in melanoma cells and required for melanomagenesis. While PHGDH amplification explained PHGDH overexpression in a subset of melanomas, oncogenic
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ACE2 Enhances Sensitivity to PD-L1 Blockade by Inhibiting Macrophage-Induced Immunosuppression and Angiogenesis Cancer Res. (IF 12.5) Pub Date : 2024-11-04 Peiyi Xie, Lei Guo, Qiang Yu, Yufei Zhao, Mincheng Yu, Hui Wang, Mengyuan Wu, Wenxin Xu, Min xu, Xiao-Dong Zhu, Yongfeng Xu, Yong-Sheng Xiao, Cheng Huang, Jian Zhou, Jia Fan, Mien-Chie Hung, Huichuan Sun, Qing-Hai Ye, Bo Zhang, Hui Li
Anti-PD-L1-based combination immunotherapy has become the first-line treatment for unresectable hepatocellular carcinoma (HCC). However, the objective response rate is lower than 40%, highlighting the need to identify mechanisms of tolerance to immune checkpoint inhibitors and accurate biomarkers of response. Here, we employed next-generation sequencing to analyze HCC samples from 10 patients receiving
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PRDM16 Induces Methylation of FLT3 to Promote FLT3-ITD Signaling and Leukemia Progression Cancer Res. (IF 12.5) Pub Date : 2024-11-04 Fengxian Zhai, Guozheng Pan, Lei Xue, Can Cheng, Jiabei Wang, Yao Liu, Lianxin Liu
Internal tandem duplication (ITD) in the FMS-like receptor tyrosine kinase-3 (FLT3) is one of the most frequent mutations in acute myeloid leukemia (AML) and is associated with poor prognosis. FLT3-ITD mutations result in endoplasmic reticulum (ER) retention and constitutive autophosphorylation of FLT3. The PR/SET domain 16 (PRDM16) is highly expressed in FLT3-ITD+ AML patients, suggesting it might
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FOXR2 targets LHX6+/DLX+ neural lineages to drive CNS neuroblastoma Cancer Res. (IF 12.5) Pub Date : 2024-11-04 Selin Jessa, Antonella De Cola, Bhavyaa Chandarana, Michael McNicholas, Steven Hébert, Adam Ptack, Damien Faury, Jessica W. Tsai, Andrey Korshunov, Timothy N. Phoenix, Benjamin Ellezam, David T W. Jones, Michael D. Taylor, Pratiti Bandopadhayay, Manav Pathania, Nada Jabado, Claudia L. Kleinman
Central nervous system neuroblastoma with FOXR2 activation (NB-FOXR2) is a high-grade tumor of the brain hemispheres and a newly identified molecular entity. Tumors express dual neuronal and glial markers, leading to frequent misdiagnoses, and limited information exists on the role of FOXR2 in their genesis. To identify their cellular origins, we profiled the transcriptomes of NB-FOXR2 tumors at the
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ASCL1 Drives the Development of Neuroendocrine Prostate Cancer Cancer Res. (IF 12.5) Pub Date : 2024-11-04 Caden N. McQuillen, Nicholas J. Brady
Therapeutic resistance to androgen receptor (AR)–targeting agents remains a significant clinical problem during the treatment of prostate cancer, with the incidence rate of resistant disease increasing as more men are treated with next-generation AR-targeted therapies. Lineage plasticity and progression to neuroendocrine prostate cancer (NEPC) are mechanisms by which prostate tumors lose dependence
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Pancreatic Cancer-Associated Fibroblasts: Where Do We Go from Here? Cancer Res. (IF 12.5) Pub Date : 2024-11-04 Eileen S Carpenter,Debora Barbosa Vendramini-Costa,Marie C Hasselluhn,Anirban Maitra,Kenneth P Olive,Edna Cukierman,Marina Pasca di Magliano,Mara H Sherman
Pancreatic ductal adenocarcinoma is a deadly disease and is projected to become the second leading cause of cancer-related death by 2030. A major hallmark is the exuberant host response comprising the tumor microenvironment, of which, cancer-associated fibroblasts (CAF) are a prevalent component. Despite the gains in understanding of their heterogeneity and functionality from CAF studies in recent
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H4K20me3-Mediated Repression of Inflammatory Genes is a Characteristic and Targetable Vulnerability of Persister Cancer Cells Cancer Res. (IF 12.5) Pub Date : 2024-10-30 Valentina Ramponi, Laia Richart, Marta Kovatcheva, Camille Stephan-Otto Attolini, Jordi Capellades, Alice E. Lord, Oscar Yanes, Gabriella Ficz, Manuel Serrano
Anti-cancer therapies can induce cellular senescence, which is highly stable, or drug-tolerant persistence, which is efficiently reversed upon therapy termination. While approaches to target senescent cells have been extensively studied, further understanding of the processes regulating persistence is needed to develop treatment strategies to suppress persister cell survival. Here, we used mTOR/PI3K
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Pharmacological blockade of a pioneer transcription factor Cancer Res. (IF 12.5) Pub Date : 2024-10-30 Katerina Cermakova, H. Courtney Hodges
Cancers frequently co-opt lineage-specific transcription factors (TFs) utilized in normal development to sustain proliferation. However, the effects of these TFs on tumor development depend considerably on where in the genome they bind. A new paper by Taylor and colleagues expands on previously developed diamidine compounds that obstruct the DNA binding sites of the pioneer TF PU.1 (SPI1) in acute
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The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma Cancer Res. (IF 12.5) Pub Date : 2024-10-30 Praneeth Reddy Sudalagunta, Rafael R. Canevarolo, Mark B. Meads, Maria Silva, Xiaohong Zhao, Christopher L. Cubitt, Samer S. Sansil, Gabriel DeAvila, Raghunandan Reddy Alugubelli, Ryan T. Bishop, Alexandre Tungesvik, Qi Zhang, Oliver Hampton, Jamie K. Teer, Eric A. Welsh, Sean J. Yoder, Bijal D. Shah, Lori Hazlehurst, Robert A. Gatenby, Dane R. Van Domelen, Yi Chai, Feng Wang, Andrew DeCastro, Amanda
Several therapeutic agents have been approved for treating multiple myeloma (MM), a cancer of bone marrow resident plasma cells. Predictive biomarkers for drug response could help guide clinical strategies to optimize outcomes. Here, we present an integrated functional genomic analysis of tumor samples from MM patients that were assessed for their ex vivo drug sensitivity to 37 drugs, clinical variables
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Distant Metastases of Breast Cancer Resemble Primary Tumors in Cancer Cell Composition but Differ in Immune Cell Phenotypes Cancer Res. (IF 12.5) Pub Date : 2024-10-22 Laura Kuett, Alina Bollhagen, Sandra Tietscher, Bettina Sobottka, Nils Eling, Zsuzsanna Varga, Holger Moch, Natalie de Souza, Bernd Bodenmiller
Breast cancer is the most commonly diagnosed cancer in women, with distant metastasis being the main cause of breast cancer-related deaths. Elucidating the changes in the tumor and immune ecosystems that are associated with metastatic disease is essential to improve understanding and ultimately treatment of metastasis. Here, we developed an in-depth, spatially resolved single-cell atlas of the phenotypic
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SOS1 Inhibition Enhances the Efficacy of KRASG12C Inhibitors and Delays Resistance in Lung Adenocarcinoma Cancer Res. (IF 12.5) Pub Date : 2024-10-22 Brianna R. Daley, Nancy E. Sealover, Bridget A. Finniff, Jacob M. Hughes, Erin Sheffels, Daniel Gerlach, Marco H. Hofmann, Kaja Kostyrko, Joseph P. LaMorte, Amanda Linke, Zaria Beckley, Andrew M. Frank, Robert E. Lewis, Matthew D. Wilkerson, Clifton Dalgard, Robert L. Kortum
The clinical effectiveness of KRASG12C inhibitors (G12Ci) is limited both by intrinsic and acquired resistance, necessitating the development of combination approaches. Here, we identified targeting proximal receptor tyrosine kinase (RTK) signaling using the SOS1 inhibitor (SOS1i) BI-3406 as a strategy to improve responses to G12Ci treatment. SOS1i enhanced the efficacy of G12Ci and limited rebound
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AKT and the Hallmarks of Cancer Cancer Res. (IF 12.5) Pub Date : 2024-10-22 Eleonora Sementino, Dalal Hassan, Alfonso Bellacosa, Joseph R. Testa
Nearly a quarter century ago, Hanahan and Weinberg conceived six unifying principles explaining how normal cells transform into malignant tumors. Their provisional set of biological capabilities acquired during tumor development cancer hallmarks would evolve to fourteen tenets as knowledge of cancer genomes, molecular mechanisms, and the tumor microenvironment expanded, most recently adding four
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Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR-ABL-Positive Leukemia Cancer Res. (IF 12.5) Pub Date : 2024-10-22 Ziwei Luo, Chencen Lin, Chuwei Yu, Changxian Yuan, Wenyong Wu, Xiaowei Xu, Renhong Sun, Yan Jia, yafang wang, Jie Shen, Dingyan Wang, Sinan Wang, Hualiang Jiang, Biao Jiang, Xiaobao Yang, Chengying Xie
SOS1 is an essential guanine nucleotide exchange factor for RAS that also plays a critical role in the activation of the small GTPase RAC mediated by BCR-ABL in leukemogenesis. Despite this, small molecule inhibitors targeting SOS1 have shown limited efficacy in clinical trials for KRAS mutant cancers, and their potential as a therapeutic approach for chronic myeloid leukemia (CML) remains largely
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Ephrin A1 Stimulates CCL2 Secretion to Facilitate Pre-metastatic Niche Formation and Promote Gastric Cancer Liver Metastasis Cancer Res. (IF 12.5) Pub Date : 2024-10-16 Yun Cui, Yongxia Chang, Xixi Ma, Meng Sun, Yuliang Huang, Feng Yang, Shuang Li, Wei Zhuo, Wei Liu, Bo Yang, Aifu Lin, Guangshuo Ou, Yuehong Yang, Shanshan Xie, Tianhua Zhou
The liver is a primary target for distal metastasis of gastric cancer (GC). The hepatic pre-metastatic niche (PMN) facilitates crucial communications between primary tumor and liver, thereby playing an essential role in hepatic metastasis. Identification of the molecular mechanisms driving PMN formation in GC could facilitate development of strategies to prevent and treat liver metastasis. Here, we
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KRAS Loss of Heterozygosity Promotes MAPK-Dependent Pancreatic Ductal Adenocarcinoma Initiation and Induces Therapeutic Sensitivity to MEK Inhibition Cancer Res. (IF 12.5) Pub Date : 2024-10-16 Sigrid K. Fey, Arafath K. Najumudeen, Dale M. Watt, Laura M. Millett, Catriona A. Ford, Kathryn Gilroy, Rosalin J. Simpson, Kathy McLay, Rosanna Upstill-Goddard, David Chang, William Clark, Colin Nixon, Joanna L. Birch, Simon T. Barry, Jennifer P. Morton, Andrew D. Campbell, Owen J. Sansom
Pancreatic cancer is characterized by the prevalence of oncogenic mutations in KRAS. Previous studies have reported that altered KRAS gene dosage drives progression and metastasis in pancreatic cancer. While the role of oncogenic KRAS mutations is well characterized, the relevance of the partnering wild-type KRAS allele in pancreatic cancer is less well understood and controversial. Using in vivo mouse
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The EP3–ZNF488 Axis Promotes Self-Renewal of Glioma Stem-like Cells to Induce Resistance to Tumor Treating Fields Cancer Res. (IF 12.5) Pub Date : 2024-10-16 Dongjiang Chen, Son B. Le, Harshit Manektalia, Tianyi Liu, Tarun E. Hutchinson, Adam O'Dell, Bodour Salhia, David D. Tran
Tumor Treating Fields (TTFields) employ low-intensity, alternating electric fields to exert antitumor activity and have demonstrated efficacy against multiple cancers, including glioblastoma (GBM). Unfortunately, cancer cells inevitably develop resistance to TTFields, highlighting the need to elucidate the underlying mechanisms to develop approaches to induce durable responses. Using a gene network-based
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Replication Stress is an Actionable Genetic Vulnerability in Desmoplastic Small Round Cell Tumors Cancer Res. (IF 12.5) Pub Date : 2024-10-16 Asuka Kawai-Kawachi, Madison M. Lenormand, Clémence Astier, Noé Herbel, Meritxell B. Cutrona, Carine Ngo, Marlène Garrido, Thomas Eychenne, Nicolas Dorvault, Laetitia Bordelet, Fei Fei Song, Ryme Bouyakoub, Anastasia Loktev, Antonio Romo-Morales, Clémence Henon, Léo Colmet-Daage, Julien Vibert, Marjorie Drac, Rachel Brough, Etienne Schwob, Oliviano Martella, Guillaume Pinna, Janet M. Shipley, Sibylle
Desmoplastic small round cell tumor (DSRCT) is an aggressive sarcoma subtype that is driven by the EWS-WT1 chimeric transcription factor. The prognosis for DSRCT is poor, and major advances in treating DSCRT have not occurred for over two decades. To identify effective therapeutic approaches to target DSRCT, we conducted a high-throughput drug sensitivity screen in a DSRCT cell line assessing chemosensitivity
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Breast Cancer Disseminated Tumor Cells: Do They Stay and Fight or Run and Hide? Cancer Res. (IF 12.5) Pub Date : 2024-10-15 Frank C. Cackowski, Hasan Korkaya
Many solid tumors including breast cancer can exhibit early dissemination and dormancy—in which cancer cells spread early in the disease process and survive long periods without detectable growth. These early disseminated tumor cells sometimes reactivate and lead to incurable metastatic disease years or even decades after curative-intent therapy for the primary tumor. We are just beginning to understand
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The USP1 Inhibitor KSQ-4279 Overcomes PARP Inhibitor Resistance in Homologous Recombination–Deficient Tumors Cancer Res. (IF 12.5) Pub Date : 2024-10-15 Louise Cadzow, Jehrod Brenneman, Erica Tobin, Pamela Sullivan, Sumeet Nayak, Janid A. Ali, Sol Shenker, Jim Griffith, Michael McGuire, Paula Grasberger, Yuji Mishina, Morgan Murray, Anne E. Dodson, Hugh Gannon, Elsa Krall, Jeff Hixon, Edmond Chipumuro, Kerstin Sinkevicius, Prafulla C. Gokhale, Suthakar Ganapathy, Ursula A. Matulonis, Joyce F. Liu, Andrew Olaharski, Dipen Sangurdekar, Hanlan Liu, Jeremy
Defects in DNA repair pathways play a pivotal role in tumor evolution and resistance to therapy. At the same time, they create vulnerabilities that render tumors dependent on the remaining DNA repair processes. This phenomenon is exemplified by the clinical activity of PARP inhibitors in tumors with homologous recombination (HR) repair defects, such as tumors with inactivating mutations in BRCA1 or
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C-Reactive Protein Induces Immunosuppression by Activating FcγR2B in Pulmonary Macrophages to Promote Lung Metastasis Cancer Res. (IF 12.5) Pub Date : 2024-10-10 Jun-Rui Feng, Xue Li, Cong Han, Yue Chang, Yu Fu, Gong-Chang Feng, Yutiantian Lei, Hai-Yun Li, Patrick Ming-Kuen Tang, Shang-Rong Ji, Yuzhu Hou, Yi Wu
C-reactive protein (CRP) is a liver-derived acute phase reactant that is a clinical marker of inflammation associated with poor cancer prognosis. Elevated CRP levels are observed in many types of cancer and are associated with significantly increased risk of metastasis, suggesting that CRP could have pro-metastatic actions. Here, we reported that CRP promotes lung metastasis by dampening the anti-cancer
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SpatialDeX is a Reference-Free Method for Cell Type Deconvolution of Spatial Transcriptomics Data in Solid Tumors Cancer Res. (IF 12.5) Pub Date : 2024-10-10 Xinyi Liu, Gongyu Tang, Yuhao Chen, Yuanxiang Li, Hua Li, Xiaowei Wang
The rapid development of spatial transcriptomics (ST) technologies has enabled transcriptome-wide profiling of gene expression in tissue sections. Despite the emergence of single-cell resolution platforms, most ST sequencing studies still operate at a multi-cell resolution. Consequently, deconvolution of cell identities within the spatial spots has become imperative for characterizing cell type-specific
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Stimulating Soluble Guanylyl Cyclase with the Clinical Agonist Riociguat Restrains the Development and Progression of Castration-Resistant Prostate Cancer Cancer Res. (IF 12.5) Pub Date : 2024-10-10 Ling Zhang, Clara I. Troccoli, Beatriz Mateo-Victoriano, Laura Misiara Lincheta, Erin Jackson, Ping Shu, Trisha Plastini, Wensi Tao, Deukwoo Kwon, X. Steven. Chen, Janaki Sharma, Merce Jorda, Surinder Kumar, David B. Lombard, James L. Gulley, Marijo Bilusic, Albert C. Lockhart, Annie Beuve, Priyamvada Rai
Castration-resistant prostate cancer (CRPC) is incurable and fatal, making prostate cancer the second-leading cancer-related cause of death for American men. CRPC results from therapeutic resistance to standard-of-care androgen deprivation (AD) treatments, through incompletely understood molecular mechanisms, and lacks durable therapeutic options. Here, we identified enhanced soluble guanylyl cyclase
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LSD1 and CoREST2 Potentiate STAT3 Activity to Promote Enteroendocrine Cell Differentiation in Mucinous Colorectal Cancer Cancer Res. (IF 12.5) Pub Date : 2024-10-04 Christopher A. Ladaika, Ahmed H. Ghobashi, William C. Boulton, Samuel A. Miller, Heather M. O'Hagan
Neuroendocrine cells have been implicated in therapeutic resistance and worse overall survival in many cancer types. Mucinous colorectal cancer (mCRC) is uniquely enriched for enteroendocrine cells (EECs), the neuroendocrine cell of the normal colon epithelium, as compared to non-mCRC. Therefore, targeting EEC differentiation may have clinical value in mCRC. Here, single cell multi-omics uncovered
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Tumor evolution reconstruction is heavily influenced by algorithmic and experimental choices Cancer Res. (IF 12.5) Pub Date : 2024-10-02 Rija Zaidi, Simone Zaccaria
Tumor progression is an evolutionary process during which cells acquire distinct genetic alterations. Several cancer evolutionary studies reconstruct this evolutionary process by applying bulk DNA sequencing to a tumor sample to infer the presence of genetic alterations using various tumor evolutionary algorithms. Through a comprehensive benchmarking effort of these algorithms, a recent study by Salcedo
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HIF1α Counteracts TGFβ1-Driven TSP1 Expression in Endothelial Cells to Stimulate Angiogenesis in the Hypoxic Tumor Microenvironment Cancer Res. (IF 12.5) Pub Date : 2024-10-02 Yu-Wei Luo, Yang Fang, Hui-Xian Zeng, Yu-Chen Ji, Meng-Zhi Wu, Hui Li, Jie-Ying Chen, Li-Min Zheng, Jian-Hong Fang, Shi-Mei Zhuang
Emerging evidence suggests that transforming growth factor β1 (TGFβ1) can inhibit angiogenesis, contradicting the coexistence of active angiogenesis and high abundance of TGFβ1 in the tumor microenvironment. Here, we investigated how tumors overcome the anti-angiogenic effect of TGFβ1. TGFβ1 treatment suppressed physiological angiogenesis in chick chorioallantoic membrane and zebrafish models but did
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Induction of the TEAD Co-activator VGLL1 by Estrogen Receptor-Targeted Therapy Drives Resistance in Breast Cancer Cancer Res. (IF 12.5) Pub Date : 2024-10-02 Carolina Gemma, Chun-Fui Lai, Anup K. Singh, Antonino Belfiore, Neil Portman, Heloisa Z. Milioli, Manikandan Periyasamy, Sara Raafat, Alyssa J. Nicholls, Claire M. Davies, Naina R. Patel, Georgia M. Simmons, Hailing Fan, Van T.M. Nguyen, Luca Magnani, Emad Rakha, Lesley-Ann Martin, Elgene Lim, R. Charles Coombes, Giancarlo Pruneri, Laki Buluwela, Simak Ali
Resistance to endocrine therapies (ET) is common in estrogen receptor (ER) positive breast cancer, and most relapsed patients die with ET-resistant disease. While genetic mutations provide explanations for some relapses, mechanisms of resistance remain undefined in many cases. Drug-induced epigenetic reprogramming has been shown to provide possible routes to resistance. By analyzing histone H3 lysine
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Resistance Management for Cancer: Lessons from Farmers Cancer Res. (IF 12.5) Pub Date : 2024-10-02 Sareh Seyedi, Valerie K. Harris, Stefania E. Kapsetaki, Shrinath Narayanan, Daniel Saha, Zachary Compton, Rezvan Yousefi, Alexander May, Efe Fakir, Amy M. Boddy, Marco Gerlinger, Christina Wu, Lida Mina, Silvie Huijben, Dawn H. Gouge, Luis Cisneros, Peter C. Ellsworth, Carlo C. Maley
One of the main reasons we have not been able to cure cancers is that treatments select for drug-resistant cells. Pest managers face similar challenges with pesticides selecting for pesticide-resistant insects, resulting in similar mechanisms of resistance. Pest managers have developed ten principles that could be translated to controlling cancers: (1) prevent onset, (2) monitor continuously, (3) identify
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Impact of Structural Racism and Social Determinants of Health on Disparities in Breast Cancer Mortality Cancer Res. (IF 12.5) Pub Date : 2024-10-02 Mary Falcone, Bodour Salhia, Chanita Hughes Halbert, Evanthia T. Roussos Torres, Daphne Stewart, Mariana C. Stern, Caryn Lerman
The striking ethnic and racial disparities in breast cancer mortality are not explained fully by pathological or clinical features. Structural racism contributes to adverse conditions that promote cancer inequities, but the pathways by which this occurs are not fully understood. Social determinants of health (SDOH), such as economic status and access to care, account for a portion of this variability
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The Next Frontier for Colorectal Cancer Screening: Blood-Based Tests Cancer Res. (IF 12.5) Pub Date : 2024-10-01 Christian Rolfo, Alessandro Russo
Colorectal cancer is associated with substantial morbidity and mortality worldwide. Detection of early colorectal cancer is possible through approved screening tests but overall adherence is quite low. Implementation of effective noninvasive options could increase screening uptake and prevent a significant number of deaths. Noninvasive early cancer detection can potentially be achieved using a liquid
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Retraction: mda-9/Syntenin Regulates the Metastatic Phenotype in Human Melanoma Cells by Activating Nuclear Factor-κB. Cancer Res. (IF 12.5) Pub Date : 2024-10-01 Habib Boukerche,Zao-Zhong Su,Luni Emdad,Devanand Sarkar,Paul B Fisher
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A Prime-Boost Vaccination Approach Induces Lung Resident Memory CD8+ T Cells Derived from Central Memory T Cells That Prevent Tumor Lung Metastasis Cancer Res. (IF 12.5) Pub Date : 2024-10-01 Haoran Xu, Ming Yue, Runhong Zhou, Pui Wang, Michael Yik-Chun Wong, Jinlin Wang, Huarong Huang, Bohao Chen, Yufei Mo, Rachel Chun-Yee Tam, Biao Zhou, Zhenglong Du, Haode Huang, Li Liu, Zhiwu Tan, Kwok-Yung Yuen, Youqiang Song, Honglin Chen, Zhiwei Chen
Memory T cells play a key role in immune protection against cancer. Vaccine-induced tissue-resident memory T (TRM) cells in the lung have been shown to protect against lung metastasis. Identifying the source of lung TRM cells can help to improve strategies, preventing tumor metastasis. Here, we found that a prime-boost vaccination approach using intramuscular DNA vaccine priming, followed by intranasal
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Remembering Hypoxia: Uncovering the Long-Term Effects of Transient Oxygen Deprivation on IFN Signaling and Progression of Breast Cancer Cancer Res. (IF 12.5) Pub Date : 2024-10-01 Stephen Connor Purdy, Heide L. Ford
Hypoxia occurs in 90% of solid tumors and is strongly associated with an increased propensity for metastasis. Hypoxia induces tumor progression largely through inducing HIF-mediated transcription, resulting in alterations to tumor cell metabolism, as well as increases in migration and invasion. Hypoxia also results in a myriad of changes to the tumor microenvironment (TME). While many studies have
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TCTN1 Induces Fatty Acid Oxidation to Promote Melanoma Metastasis Cancer Res. (IF 12.5) Pub Date : 2024-09-26 Yinlam Li, Ren Ming, Tianyi Zhang, Zixu Gao, Lu Wang, Yang Yang, Kangjie Shen, Chenlu Wei, Yu Zhu, Jianrui Li, Shaoluan Zheng, Zucheng Luo, Yiteng Ding, Jiangying Xuan, Qianrong Hu, Yanwen Yang, Jianying Gu, Chuanyuan Wei
Metabolic reprogramming promotes and sustains multiple steps of melanoma metastasis. Identification of key regulators of metabolic reprogramming could lead to the development of treatments for preventing and treating metastatic melanoma. Here, we identified that the tectonic family member TCTN1 promotes melanoma metastasis by increasing fatty acid oxidation (FAO). In clinical melanoma samples, high
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The Genomic Landscape of Benign and Malignant Thyroid Tumors from Individuals Carrying Germline PTEN Variants Is Distinct from Sporadic Thyroid Cancers Cancer Res. (IF 12.5) Pub Date : 2024-09-24 Gilman Plitt, Takae Brewer, Lamis Yehia, Laura Rabinowitz, Christopher C. Griffith, Charis Eng
Patients with PTEN hamartoma tumor syndrome (PHTS), a molecular diagnosis for those carrying germline PTEN pathogenic variants, have a high prevalence of benign and malignant thyroid disease. Characterizing the genomic landscape in PHTS thyroid tumors could provide insights into malignant potential and tumor progression to help optimize diagnosis, surveillance, and treatment in this population. To
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Targeting SHCBP1 Inhibits Tumor Progression by Restoring Ciliogenesis in Ductal Carcinoma Cancer Res. (IF 12.5) Pub Date : 2024-09-23 Wengui Shi, Lianshun Li, Huiming Zhao, Zhengyang Li, Zhijian Ma, Qianlin Gu, Huili Ye, Xiangyan Jiang, Yuman Dong, Long Qin, Huinian Zhou, Zeyuan Yu, Zuoyi Jiao
Primary cilia detect and transmit environmental signals into cells. Primary cilia are absent in a subset of ductal carcinomas characterized by distinctive biological activities, and recovery of cilia with normal functionality has been shown to have therapeutic potential in some cancer types. Therefore, elucidation of the underlying mechanism and clinical significance of ciliary loss in ductal carcinomas
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Selective Enhancer Gain of Function Deregulates MYC Expression in Multiple Myeloma Cancer Res. (IF 12.5) Pub Date : 2024-09-23 Mahshid Rahmat, Kendell Clement, Jean-Baptiste Alberge, Romanos Sklavenitis-Pistofidis, Rohan Kodgule, Charles P. Fulco, Daniel Heilpern-Mallory, Katarina Nilsson, David Dorfman, Jesse M. Engreitz, Gad Getz, Luca Pinello, Russell Ryan, Irene M. Ghobrial
MYC deregulation occurs in the majority of multiple myeloma (MM) cases and is associated with progression and worse prognosis. Enhanced MYC expression occurs in about 70% of MM patients, but it is known to be driven by translocation or amplification events in only ~40% of myelomas. Here, we used CRISPR interference (CRISPRi) to uncover an epigenetic mechanism of MYC regulation whereby increased accessibility
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The Innate Immune System and TRAIL-BCL-XL Axis Mediate a Sex Bias in Lung Cancer and Confer a Therapeutic Vulnerability in Females Cancer Res. (IF 12.5) Pub Date : 2024-09-23 Lauren May, Bin Hu, Preksha Jerajani, Akash Jagdeesh, Ohud Alhawiti, Lillian Cai, Nina Semenova, Chunqing Guo, Madison Isbell, Xiaoyan Deng, Anthony Faber, Raghavendra Pillappa, Dipankar Bandyopadhyay, Xiang-Yang Wang, Alexander Neuwelt, Jennifer Koblinski, Paula D. Bos, Howard Li, Rebecca Martin, Joseph W. Landry
There is a significant sex-bias in lung cancer with males showing increased mortality compared to females. A better mechanistic understanding of these differences could help identify therapeutic targets to personalize cancer therapies to each sex. After observing a clear sex-bias in humanized mice, with male patient-derived xenograft (PDX) lung tumors being more progressive and deadlier than female
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Single-cell Transcriptomic Analysis Identifies Senescent Osteocytes that Trigger Bone Destruction in Breast Cancer Metastasis Cancer Res. (IF 12.5) Pub Date : 2024-09-23 Japneet Kaur, Manish Adhikari, Hayley M. Sabol, Aric Anloague, Sharmin Khan, Noriyoshi Kurihara, Marta Diaz-delCastillo, Christina Møller. Andreasen, C. Lowry Barnes, Jeffrey B. Stambough, Michela Palmieri, Olivia Reyes-Castro, Jennifer Zarrer, Hanna Taipaleenmäki, Elena Ambrogini, Maria Almeida, Charles O'Brien, Intawat Nookaew, Jesus Delgado-Calle
Breast cancer bone metastases increase fracture risk and are a major cause of morbidity and mortality among women. Upon colonization by tumor cells, the bone microenvironment undergoes profound reprogramming to support cancer progression, which disrupts the balance between osteoclasts and osteoblasts and leads to bone lesions. A deeper understanding of the processes mediating this reprogramming could
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Lipid-laden macrophages recycle myelin to feed glioblastoma. Cancer Res. (IF 12.5) Pub Date : 2024-09-18 Lizhi Pang,Fei Zhou,Peiwen Chen
Tumor-associated microglia and macrophages (TAMs) make up the largest immune cell population in the glioblastoma (GBM) tumor microenvironment (TME). Given the heterogeneity and plasticity of TAMs in the GBM TME, understanding the context-dependent cancer cell-TAM symbiotic interaction is crucial for understanding GBM biology and developing effective therapies. In a recent issue of Cell, Kloosterman
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A Paradigm Shift in Tumor Immunology: Th17 Cells and TGF-β in Intestinal Cancer Initiation Cancer Res. (IF 12.5) Pub Date : 2024-09-18 Megan M. Wyatt, Chrystal M. Paulos
Cancer remains one of the most complex challenges in modern medicine, with intricate relationships between immune responses and tumor development. This article examines a groundbreaking study by Fesneau, Thevin and colleagues, published in Nature Immunology. This elegant body of work explores the link between chronic inflammation and cancer, particularly focusing on Th17 cells involved in intestinal
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Inhibition of JNK Signaling Overcomes Cancer-Associated Fibroblast-Mediated Immunosuppression and Enhances the Efficacy of Immunotherapy in Bladder Cancer Cancer Res. (IF 12.5) Pub Date : 2024-09-18 Chengying Cui, Haojie Zhang, Congcong Yang, Mingwei Yin, Xinkun Teng, Miaomiao Yang, Dejie Kong, Jinzhi Zhang, Weidong Peng, Zhimin Chu, Jingjing Wang, Yating Sun, Liping Kang, Bin Lyu, Qian Gao, Mingqing Wu, Yongqiang Wang, Yang Li
Currently, only 20-40% of cancer patients benefit from immune checkpoint inhibitors. Understanding the mechanisms underlying the immunosuppressive tumor microenvironment (TME) and characterizing dynamic changes in the immunological landscape during treatment are critical for improving responsiveness to immunotherapy. Here, we identified JNK signaling in cancer-associated fibroblasts (CAFs) as a regulator
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mLumiOpto is a Mitochondrial-Targeted Gene Therapy for Treating Cancer Cancer Res. (IF 12.5) Pub Date : 2024-09-17 Kai Chen, Patrick Ernst, Anusua Sarkar, Seulhee Kim, Yingnan Si, Tanvi Varadkar, Matthew D. Ringel, Xiaoguang Liu, Lufang Zhou
Mitochondria are important in various aspects of cancer development and progression. Targeting mitochondria in cancer cells holds great therapeutic promise, yet current strategies to specifically and effectively destroy cancer mitochondria in vivo are limited. Here, we developed mLumiOpto, an innovative mitochondrial-targeted luminoptogenetics gene therapy designed to directly disrupt the inner mitochondrial
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CircRREB1 Mediates Metabolic Reprogramming and Stemness Maintenance to Facilitate Pancreatic Ductal Adenocarcinoma Progression Cancer Res. (IF 12.5) Pub Date : 2024-09-17 Zeyin Rong, Jin Xu, Jianhui Yang, Wei Wang, Rong Tang, Zifeng Zhang, Zhen Tan, Qingcai Meng, Jie Hua, Jiang Liu, Bo Zhang, Chen Liang, Xianjun Yu, Si Shi
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumor with limited treatment options and poor patient survival. Circular RNAs (circRNAs) play crucial regulatory roles in the occurrence and development of various cancers, including PDAC. Here, using circRNA sequencing of diverse PDAC samples, we identified circRREB1 as an oncogenic circRNA that is significantly upregulated in PDAC and is
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Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer Cancer Res. (IF 12.5) Pub Date : 2024-09-17 Koki Oyama, Kohei Nakata, Chikanori Tsutsumi, Masataka Hayashi, Bo Zhang, Yuki Mochida, Tomohiko Shinkawa, Kento Hirotaka, Pingshan Zhong, Satomi Date, Haizhen Luo, Akihiro Kubo, Nobuhiro Higashijima, Yutaka Yamada, Toshiya Abe, Noboru Ideno, Kazuhiro Koikawa, Chika Iwamoto, Naoki Ikenaga, Kenoki Ohuchida, Hideya Onishi, Takashi Morisaki, Keiji Kuba, Yoshinao Oda, Masafumi Nakamura
The effect of immune checkpoint inhibitors is extremely limited in patients with pancreatic ductal adenocarcinoma (PDAC) due to the suppressive tumor immune microenvironment (TIME). Autophagy, which has been shown to play a role in anti-tumor immunity, has been proposed as a therapeutic target for PDAC. Here, single-cell RNA-sequencing of autophagy-deficient murine PDAC tumors revealed that autophagy
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Precise In Situ Delivery of a Photo-enhanceable Inflammasome-Activating Nanovaccine Activates Anti-cancer Immunity Cancer Res. (IF 12.5) Pub Date : 2024-09-17 Yang Zhou, Li Pang, Tao Ding, Kang Chen, Jinzhao Liu, Meicen Wu, Weiping Wang, Kwan Man
A variety of state-of-the-art nanovaccines (NVs) combined with immunotherapies have recently been developed to treat malignant tumors, showing promising results. However, immunosuppression in the tumor microenvironment (TME) restrains cytotoxic T cells infiltration and limits the efficacy of immunotherapies in solid tumors. Therefore, tactics for enhancing antigen cross-presentation and reshaping the
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CD24-Targeted NIR-II Fluorescence Imaging Enables Early Detection of Colorectal Neoplasia Cancer Res. (IF 12.5) Pub Date : 2024-09-17 Xiaoyong Guo, Shuangling Luo, Xiaofeng Wang, Yingying Cui, Miaomiao Li, Zeyu Zhang, Lidan Fu, Caiguang Cao, Xiaojing Shi, Haifeng Liu, Yawei Qu, Xiangyu Gao, Zhenhua Hu, Jie Tian
Colorectal cancer (CRC) continues to be a major health issue even though screening methods have facilitated early detection. Despite the high sensitivity of white-light colonoscopy, it frequently overlooks invasive flat or depressed lesions, which can lead to the development of larger, advanced tumors. Fluorescence molecular imaging (FMI) offers a promising approach for early tumor detection by targeting
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Cancer-Associated Fibroblasts: From Spectators to Protagonists in Pancreatic Cancer Progression. Cancer Res. (IF 12.5) Pub Date : 2024-09-16 Gianluca Mucciolo,Wenlong Li,Giulia Biffi
Our knowledge of the origins, heterogeneity, and functions of cancer-associated fibroblasts (CAF) in pancreatic ductal adenocarcinoma (PDAC) has exponentially increased over the last two decades. This has been facilitated by the implementation of new models and single-cell technologies. However, a few key studies preceded the current exciting times in CAF research and were fundamental in initiating
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Nutrient Levels and Nutrient Sources in Pancreatic Tumors. Cancer Res. (IF 12.5) Pub Date : 2024-09-16 Sven Groessl,Wilhelm Palm
It has been known that poor tumor perfusion and dysregulated cancer cell metabolism give rise to tumor microenvironments with unphysiologic nutrient levels, but the precise alterations in metabolite abundance are not well defined. In a 2015 study in Cancer Research, Kamphorst and colleagues published a detailed comparison of the metabolome from human pancreatic tumors and benign tissues. Tumors were
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From Inception to Malignancy: the Co-evolution of Pancreatic Cancer and Its Immunosuppressive Microenvironment. Cancer Res. (IF 12.5) Pub Date : 2024-09-16 Filip Bednar,Lee Y Olsen,Marina Pasca di Magliano
Published in Cancer Research in 2007, Clark and colleagues first introduced the concept that the immune microenvironment evolves in lockstep with the progression of pancreatic cancer. Leveraging genetically engineered mouse models of the disease that were described a few years earlier, Clark and colleagues used a combination of approaches to describe the dynamics of immune evolution in precursor lesions
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Hope on the Horizon: A Revolution in KRAS Inhibition Is Creating a New Treatment Paradigm for Patients with Pancreatic Cancer. Cancer Res. (IF 12.5) Pub Date : 2024-09-16 Andrew J Aguirre,Ben Z Stanger,Anirban Maitra
KRAS is the most frequently altered oncogene in pancreatic ductal adenocarcinoma, in which the aberrantly activated RAS signaling pathway plays pleiotropic roles in tumor initiation and maintenance. Nearly four decades after the discovery of the RAS oncoprotein, a multitude of pharmacologic inhibitors are now available that directly target mutant KRAS. This In Focus commentary, published simultaneously
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Keep It Moving: Physical Activity in the Prevention of Obesity-Driven Pancreatic Cancer. Cancer Res. (IF 12.5) Pub Date : 2024-09-16 Akin Sogunro,Mandar D Muzumdar
Despite the already dire impact of pancreatic cancer, a growing subset of patients with obesity exhibits an amplified risk of disease and worse outcomes. Mouse models have revealed that obesity is distinctly pathogenic, accelerating pancreatic ductal adenocarcinoma (PDAC) progression and inducing increased desmoplasia and myeloid cell infiltration in the tumor microenvironment. However, whether and
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The Pivotal Role of Germline BRCA2 Pathogenic Variants in “Apparently Sporadic” Pancreatic Cancer Cancer Res. (IF 12.5) Pub Date : 2024-09-16 Jonathan R. Brody, Alison P. Klein
In 1996, Goggins and colleagues demonstrated the importance of germline BRCA2 pathogenic variants in the development of apparently sporadic pancreatic ductal adenocarcinoma (PDAC). Previously, the group identified homozygous deletion of the 13q region in PDACs, enabling the identification of the BRCA2 gene. This 1996 article first revealed loss of BRCA2, both germline and somatic, as a key driver of
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Targeting Fatty Acid Metabolism Abrogates the Differentiation Blockade in Pre-leukemic Cells Cancer Res. (IF 12.5) Pub Date : 2024-09-12 Xiaoyu Liu, Yu Liu, Qing Rao, Yihan Mei, Haiyan Xing, Runxia Gu, Junli Mou, Manling Chen, Fan Ding, Wanqing Xie, Kejing Tang, Zheng Tian, Min Wang, Shaowei Qiu, Jianxiang Wang
Metabolism plays a key role in the maintenance of normal hematopoietic stem cells (HSCs) and in the development of leukemia. A better understanding of the metabolic characteristics and dependencies of pre-leukemic cells could help identify potential therapeutic targets to prevent leukemic transformation. As AML1-ETO, one of the most frequent fusion proteins in acute myeloid leukemia that is encoded
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Simultaneous Targeting of NQO1 and SOD1 Eradicates Breast Cancer Stem Cells via Mitochondrial Futile Redox Cycling Cancer Res. (IF 12.5) Pub Date : 2024-09-12 Ming Luo, Na Shen, Li Shang, Zeng Fang, Ying Xin, Yuxi Ma, Min Du, Yuan Yuan, Chenchen Hu, Yun Tang, Jing Huang, Wei Wei, Myung Ryul Lee, Paul J. Hergenrother, Max S. Wicha
Triple negative breast cancer (TNBC) contains the highest proportion of cancer stem-like cells (CSCs), which display intrinsic resistance to currently available cancer therapies. This therapeutic resistance is partially mediated by an antioxidant defense coordinated by the transcription factor NRF2 and its downstream targets including NQO1. Here, we identified the antioxidant enzymes NQO1 and SOD1