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A Benzarone Derivative Inhibits EYA to Suppress Tumor Growth in SHH Medulloblastoma Cancer Res. (IF 11.2) Pub Date : 2024-03-15 Grace H. Hwang, Maria F. Pazyra-Murphy, Hyuk-Soo Seo, Sirano Dhe-Paganon, Sylwia A. Stopka, Marina DiPiazza, Nizhoni Sutter, Thomas W. Gero, Alison Volkert, Lincoln Ombelets, Georgia Dittemore, Matthew G. Rees, Melissa M. Ronan, Jennifer A. Roth, Nathalie Y.R. Agar, David A. Scott, Rosalind A. Segal
Medulloblastoma is one of the most common malignant brain tumors of children, and 30% of medulloblastomas are driven by gain-of-function genetic lesions in the Sonic Hedgehog (SHH) signaling pathway. EYA1, a haloacid dehalogenase phosphatase and transcription factor, is critical for tumorigenesis and proliferation of SHH medulloblastoma (SHH-MB). Benzarone and benzbromarone have been identified as
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NCI Cancer Research Data Commons: Cloud-based Analytical Resources Cancer Res. (IF 11.2) Pub Date : 2024-03-15 David Pot, Zelia Worman, Alexander Baumann, Shirish Pathak, Rowan Beck, Katherine Thayer, Tanja M. Davidsen, Erika Kim, Brandi Davis-Dusenbery, John Otridge, Todd Pihl, the CRDC Program, Jill S. Barnholtz-Sloan, Anthony R. Kerlavage
The NCI’s Cloud Resources (CRs) are the analytical components of the Cancer Research Data Commons (CRDC) ecosystem. This review describes how the three CRs (Broad Institute FireCloud, Institute for Systems Biology Cancer Gateway in the Cloud, and Seven Bridges Cancer Genomics Cloud) provide access and availability to large, cloud-hosted, multi-modal cancer datasets, as well as offer tools and workspaces
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NCI Cancer Research Data Commons: Resources to Share Key Cancer Data Cancer Res. (IF 11.2) Pub Date : 2024-03-15 Zhining Wang, Tanja M. Davidsen, Gina R. Kuffel, KanakaDurga Addepalli, Amanda Bell, Esmeralda Casas-Silva, Hayley Dingerdissen, Keyvan Farahani, Andrey Fedorov, Sharon Gaheen, Robert L. Grossman, Ron Kikinis, Erika Kim, John Otridge, Todd Pihl, Melissa Porter, Henry Rodriguez, Louis M. Staudt, Ratna R. Thangudu, Sudha Venkatachari, Jean Claude Zenklusen, Xu Zhang, Jill S. Barnholtz-Sloan, the CRDC
Since 2014, the National Cancer Institute (NCI) has launched a series of data commons as part of the Cancer Research Data Commons (CRDC) ecosystem housing genomic, proteomic, imaging, and clinical data to support cancer research and promote data sharing of NCI-funded studies. This review describes each data commons (Genomic Data Commons, Proteomic Data Commons, Integrated Canine Data Commons, Cancer
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FASN Inhibition Decreases MHC-I Degradation and Synergizes with PD-L1 Checkpoint Blockade in Hepatocellular Carcinoma Cancer Res. (IF 11.2) Pub Date : 2024-03-15 Jiao Huang, Wai Ying Tsang, Xiao-Na Fang, Yu Zhang, Jie Luo, Lan-Qi Gong, Bai-Feng Zhang, Ching Ngar Wong, Zhi-Hong Li, Bei-Lei Liu, Jin-Lin Huang, Yu-Ma Yang, Shan Liu, Liu-Xian Ban, Yiu Hong Chan, Xin-Yuan Guan
Immune checkpoint inhibitors (ICI) transformed the treatment landscape of hepatocellular carcinoma (HCC). Unfortunately, patients with attenuated MHC-I expression remain refractory to ICIs, and druggable targets for upregulating MHC-I are limited. Here, we found that genetic or pharmacologic inhibition of fatty acid synthase (FASN) increased MHC-I levels in HCC cells, promoting antigen presentation
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NCI Cancer Research Data Commons: Lessons Learned and Future State Cancer Res. (IF 11.2) Pub Date : 2024-03-15 Erika Kim, Tanja M. Davidsen, Brandi Davis-Dusenbery, Alexander Baumann, Angela Maggio, Zhaoyi Chen, Daoud Meerzaman, Esmeralda Casas-Silva, David Pot, Todd Pihl, John Otridge, Eve Shalley, the CRDC Program, Jill S. Barnholtz-Sloan, Anthony R. Kerlavage
More than ever, scientific progress in cancer research hinges on our ability to combine datasets and extract meaningful interpretations to better understand diseases and ultimately inform the development of better treatments and diagnostic tools. To enable the successful sharing and use of big data, the NCI developed the Cancer Research Data Commons (CRDC), providing access to a large, comprehensive
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AKTing on R Loops Makes for an ATRactive Target in Ovarian Cancer Therapy Cancer Res. (IF 11.2) Pub Date : 2024-03-15 Vijayalalitha Ramanarayanan, Philipp Oberdoerffer
High-grade serous ovarian carcinoma (HGSOC) is the deadliest subtype of ovarian cancer. While PARP inhibitors (PARPi) have transformed the care of advanced HGSOC, PARPi resistance poses a major limitation to their clinical utility. DNA damage checkpoint signaling via ATR kinase can counteract PARPi-induced replication stress, making ATR an attractive therapeutic target in PARPi-resistant tumors. However
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NCI Cancer Research Data Commons: Core Standards and Services Cancer Res. (IF 11.2) Pub Date : 2024-03-15 Arthur Brady, Amanda Charbonneau, Robert L. Grossman, Heather H. Creasy, Robinette Renner, Todd Pihl, John Otridge, Erika Kim, the CRDC Program, Jill S. Barnholtz-Sloan, Anthony R. Kerlavage
The National Cancer Institute (NCI) Cancer Research Data Commons (CRDC) is a collection of data commons, analysis platforms, and tools that make existing cancer data more findable and accessible by the cancer research community. In practice, the two biggest hurdles to finding and using data for discovery are the wide variety of models and ontologies used to describe data, and the dispersed storage
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Repolarization of immunosuppressive macrophages by targeting SLAMF7-regulated CCL2 signaling sensitizes hepatocellular carcinoma to immunotherapy Cancer Res. (IF 11.2) Pub Date : 2024-03-14 Jialei Weng, Zheng Wang, Zhiqiu Hu, Wenxin Xu, Jia-Lei Sun, Fu Wang, Qiang Zhou, Shaoqing Liu, Min Xu, Minghao Xu, Dongmei Gao, Ying-Hao Shen, Yong Yi, Yi Shi, Qiongzhu Dong, Chenhao Zhou, Ning Ren
Immune checkpoint inhibitors have limited efficacy in hepatocellular carcinoma (HCC). Macrophages are the most abundant immune cells in HCC, suggesting that a better understanding of the intrinsic processes by which tumor cells regulate macrophages could help identify strategies to improve response to immunotherapy. As signaling lymphocytic activation molecule (SLAM) family members regulate various
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Whole-genome DNA methylation profiling of intrahepatic cholangiocarcinoma reveals prognostic subtypes with distinct biological drivers Cancer Res. (IF 11.2) Pub Date : 2024-03-12 Haotian Liao, Xing Chen, Haichuan Wang, Youpei Lin, Lu Chen, Kefei Yuan, Mingheng Liao, Hanyu Jiang, Jiajie Peng, Zhenru Wu, Jiwei Huang, Jiaxin Li, Yong Zeng
Intrahepatic cholangiocarcinoma (iCCA) is the second most prevalent primary liver cancer. While the genetic characterization of iCCA has led to targeted therapies for treating tumors with FGFR2 alterations and IDH1/2 mutations, only a limited number of patients can benefit from these strategies. Epigenomic profiles have emerged as potential diagnostic and prognostic biomarkers for improving treatment
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SPARC stabilizes ApoE to induce cholesterol-dependent invasion and sorafenib resistance in hepatocellular carcinoma Cancer Res. (IF 11.2) Pub Date : 2024-03-12 Shan Wan, Quan-Yao He, Yun Yang, Feng Liu, Xue Zhang, Xin Guo, Hui Niu, Yi Wang, Yi-Xuan Liu, Wen-Long Ye, Xiu-Ming Li, Xue-Mei ZhuanSun, Pu Sun, Xiao-Shun He, Guang Hu, Kai Breuhahn, Hua Zhao, Guo-Qiang Wu, Hua Wu
Dysregulation of cholesterol homeostasis is implicated in the development and progression of hepatocellular carcinoma (HCC) that is characterized by intrahepatic and early extrahepatic metastasis. A better understanding of the underlying mechanisms regulating cholesterol metabolism in HCC could help identify strategies to circumvent the aggressive phenotype. Here, we found that high expression of intracellular
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ACSL4-mediated membrane phospholipid remodeling induces integrin β1 activation to facilitate triple-negative breast cancer metastasis Cancer Res. (IF 11.2) Pub Date : 2024-03-12 Yuxiang Qiu, Xing Wang, Yan Sun, Ting Jin, Rui Tang, Xinyue Zhou, Ming Xu, Yubi Gan, Rui Wang, Haojun Luo, Manran Liu, Xi Tang
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and has a poor prognosis and a high propensity to metastasize. Lipid metabolism has emerged as a critical regulator of tumor progression and metastasis in other cancer types. Characterization of the lipid metabolic features of TNBC could provide important insights into the drivers of TNBC metastasis. Here, we showed
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A histone methylation-MAPK signaling axis drives durable epithelial-mesenchymal transition in hypoxic pancreatic cancer Cancer Res. (IF 11.2) Pub Date : 2024-03-12 Brooke A. Brown, Paul J. Myers, Sara J. Adair, Jason R. Pitarresi, Shiv K. Sah-Teli, Logan A. Campbell, William S. Hart, Michelle C. Barbeau, Kelsey Leong, Nicholas Seyler, William Kane, Kyoung Eun Lee, Edward Stelow, Marieke Jones, M. Celeste Simon, Peppi Koivunen, Todd W. Bauer, Ben Z. Stanger, Matthew J. Lazzara
The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) plays a key role in tumor progression and response to therapy. The dense PDAC stroma causes hypovascularity, which leads to hypoxia. Here, we showed that hypoxia drives long-lasting epithelial-mesenchymal transition (EMT) in PDAC primarily through a positive-feedback histone methylation-MAPK signaling axis. Transformed cells preferentially
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Transcriptomic Profiling of Plasma Extracellular Vesicles Enables Reliable Annotation of the Cancer-specific Transcriptome and Molecular Subtype Cancer Res. (IF 11.2) Pub Date : 2024-03-07 Vahid Bahrambeigi, Jaewon J. Lee, Vittorio Branchi, Kimal I. Rajapakshe, Zhichao Xu, Naishu Kui, Jason T. Henry, Kun Wang, Bret M. Stephens, Sarah Dhebat, Mark W. Hurd, Ryan Sun, Peng Yang, Eytan Ruppin, Wenyi Wang, Scott Kopetz, Anirban Maitra, Paola A. Guerrero
Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved
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Adipose Stromal Cell–Derived Cancer-Associated Fibroblasts Suppress FGFR Inhibitor Efficacy Cancer Res. (IF 11.2) Pub Date : 2024-03-04 Mikhail G. Kolonin, Dimitris Anastassiou
Cancer aggressiveness has been linked with obesity, and studies have shown that adipose tissue can enhance cancer progression. In this issue of Cancer Research, Hosni and colleagues discover a paracrine mechanism mediated by adipocyte precursor cells through which urothelial carcinomas become resistant to erdafitinib, a recently approved therapy inhibiting fibroblast growth factor receptors (FGFR)
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Stressing Out Cancer: Chronic Stress Induces Dysbiosis and Enhances Colon Cancer Growth Cancer Res. (IF 11.2) Pub Date : 2024-03-04 Shannon E. McCollum, Yatrik M. Shah
Psychologic stress significantly impacts colorectal cancer, and chronic stress is known to decrease treatment efficacy and survival rates in patients with colorectal cancer. Previous studies have linked psychologic stress to changes in the gut microbiota, and the role of the microbiota in colorectal cancer progression is well characterized. Despite this, the mechanistic link between chronic stress
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Bile acid metabolism mediates cholesterol homeostasis and promotes tumorigenesis in clear cell renal cell carcinoma Cancer Res. (IF 11.2) Pub Date : 2024-02-28 Romain Riscal, Sarah M. Gardner, Nathan J. Coffey, Madeleine Carens, Clementina Mesaros, Jimmy P. Xu, Yizheng Xue, Leah Davis, Sara Demczyszyn, Austin Vogt, Adam Olia, Jennifer M. Finan, Jason Godfrey, David C. Schultz, Ian A. Blair, Brian Keith, Ronen Marmorstein, Nicolas Skuli, M. Celeste Simon
Clear cell renal cell carcinoma (ccRCC) incidence has risen steadily over the last decade. Elevated lipid uptake and storage is required for ccRCC cell viability. As stored cholesterol is the most abundant component in ccRCC intracellular lipid droplets, it may also play an important role in ccRCC cellular homeostasis. In support of this hypothesis, ccRCC cells acquire exogenous cholesterol through
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Mutant U2AF1-induced mis-splicing of mRNA translation genes confers resistance to chemotherapy in acute myeloid leukemia Cancer Res. (IF 11.2) Pub Date : 2024-02-28 Peng Jin, Xiaoling Wang, Qiqi Jin, Yi Zhang, Jie Shen, Ge Jiang, Hongming Zhu, Ming Zhao, Dan Wang, Zeyi Li, Yan Zhou, Wenzhu Li, Wei Zhang, Yabin Liu, Siyang Wang, Wen Jin, Yuncan Cao, Guangying Sheng, Fangyi Dong, Shishuang Wu, Xiaoyang Li, Zhen Jin, Mengke He, Xiaxin Liu, Luonan Chen, Yunxiang Zhang, Kankan Wang, Junmin Li
Patients with primary refractory acute myeloid leukemia (AML) have a dismal long-term prognosis. Elucidating the resistance mechanisms to induction chemotherapy could help identify strategies to improve AML patient outcomes. Herein, we retrospectively analyzed the multi-omics data of more than 1,500 AML cases and found that patients with spliceosome mutations had a higher risk of developing refractory
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β-catenin Activation Reprograms Ammonia Metabolism to Promote Senescence Resistance in Hepatocellular Carcinoma Cancer Res. (IF 11.2) Pub Date : 2024-02-28 Ye Wang, Chunxiao Cheng, Yanjun Lu, Zhaowu Lian, Qi Liu, Yanchao Xu, Yunzheng Li, Huan Li, Laizhu Zhang, Xiang Jiang, Binghua Li, Decai Yu
Hepatocellular carcinoma (HCC) is a typical tumor that undergoes metabolic reprogramming, differing from normal liver tissue in glucose, lipid, nucleic acid, and amino acid metabolism. While ammonia is a toxic metabolic byproduct, it has also been recently recognized as a signaling molecule to activate lipid metabolism, and it can be a nitrogen source for biosynthesis to support tumorigenesis. In this
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PRMT1 sustains de novo fatty acid synthesis by methylating PHGDH to drive chemoresistance in triple-negative breast cancer. Cancer Res. (IF 11.2) Pub Date : 2024-02-22 Takehiro Yamamoto, Tetsu Hayashida, Yohei Masugi, Kiyotaka Oshikawa, Noriyo Hayakawa, Mai Itoh, Chiyoko Nishime, Masami Suzuki, Aiko Nagayama, Yuko Kawai, Takako Hishiki, Tomomi Matsuura, Yoshiko Naito, Akiko Kubo, Arisa Yamamoto, Yujiro Yoshioka, Tomokazu Kurahori, Misa Nagasaka, Minako Takizawa, Naoharu Takano, Koji Kawakami, Michiie Sakamoto, Masatoshi Wakui, Takushi Yamamoto, Yuko Kitagawa, Yasuaki
Triple-negative breast cancer (TNBC) chemoresistance hampers the ability to effectively treat patients. Identification of mechanisms driving chemoresistance can lead to strategies to improve treatment. Here, we revealed that protein arginine methyltransferase-1 (PRMT1) simultaneously methylates D-3-phosphoglycerate dehydrogenase (PHGDH), a critical enzyme in serine synthesis, and the glycolytic enzymes
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DNA of neutrophil extracellular traps binds TMCO6 to impair CD8+ T-cell immunity in hepatocellular carcinoma. Cancer Res. (IF 11.2) Pub Date : 2024-02-21 Mengjia Song, Chaoqi Zhang, Shaoyan Cheng, Dijun Ouyang, Yu Ping, Jieying Yang, YaoJun Zhang, Yan Tang, Hao Chen, Qi-jing Wang, Yong-qiang Li, Jia He, Tong Xiang, Yizhuo Zhang, Jian-Chuan Xia
Neutrophil extracellular traps (NETs), formed by the extracellular release of decondensed chromatin and granules, have been shown to promote tumor progression and metastasis. Tumor-associated neutrophils in hepatocellular carcinoma (HCC) are prone to NET formation, highlighting the need for a more comprehensive understanding of the mechanisms of action of NETs in liver cancer. Here, we showed that
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PABPC1L induces IDO1 to promote tryptophan metabolism and immune suppression in renal cell carcinoma Cancer Res. (IF 11.2) Pub Date : 2024-02-21 Guannan Shu, Minyu Chen, Wuyuan Liao, Liangmin Fu, Mingjie Lin, Chengpeng Gui, Junjie Cen, Jun Lu, Zhenhua Chen, Jinhuan Wei, Wei Chen, Yinghan Wang, Jiangquan Zhu, Tianxin Zhao, Xiaonan Liu, Jiajia Jing, Guo-Chang Liu, Yihui Pan, Junhang Luo, Jiaxing Zhang
The tumor microenvironment (TME) in renal cell carcinomas (RCC) is marked by substantial immunosuppression and immune resistance despite having extensive T-cell infiltration. Elucidation of the mechanisms underlying immune evasion could help identify therapeutic strategies to boost the efficacy of immune checkpoint blockade (ICB) in RCC. This study uncovered a mechanism wherein the polyadenylate-binding
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Lipid-encapsulated mRNAs encoding complex fusion proteins potentiate anti-tumor immune responses Cancer Res. (IF 11.2) Pub Date : 2024-02-21 Casey W. Shuptrine, Yuhui Chen, Jayalakshmi Miriyala, Karen Lenz, Danielle Moffett, Thuy-Ai Nguyen, Jenn Michaux, Kristen Campbell, Connor Smith, Marc Morra, Yisel Rivera-Molina, Noah Murr, Sarah Cooper, Ashlyn McGuire, Vishruti Makani, Nathan Oien, Jeffrey T. Zugates, Suresh de Silva, Taylor H. Schreiber, Seymour de Picciotto, George Fromm
Lipid nanoparticle (LNP)-encapsulated mRNA has been used for in vivo production of several secreted protein classes, such as IgG, and has enabled the development of personalized vaccines in oncology. Establishing the feasibility of delivering complex multi-specific modalities that require higher-order structures important for their function could help expand the use of mRNA/LNP biologic formulations
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Exploiting tertiary lymphoid structures to stimulate antitumor immunity and improve immunotherapy efficacy Cancer Res. (IF 11.2) Pub Date : 2024-02-21 Giulia Petroni, Serena Pillozzi, Lorenzo Antonuzzo
Tumor-associated tertiary lymphoid structures (TLS) have been associated with favorable clinical outcomes and response to immune checkpoint inhibitors in many cancer types, including non-small cell lung cancer. Although the detailed cellular and molecular mechanisms underlying these clinical associations have not been fully elucidated, growing preclinical and clinical studies are helping to elucidate
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Decoding Serine Metabolism: Unveiling Novel Pathways for Evolving Cancer Therapies Cancer Res. (IF 11.2) Pub Date : 2024-02-16 Aristotle Lau, John Blenis, Guillermo Burgos-Barragan
Serine metabolism plays a pivotal role in cancer, making it an appealing therapeutic target. Two recent studies published in Nature Metabolism and Science Translational Medicine uncovered novel players and therapeutic opportunities within this crucial metabolic pathway. Papalazarou and colleagues employed genetic tools coupled with metabolomics and high-throughput imaging to identify and characterize
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Macrophages Under the Influence of Tumor Mesothelin Weaken Host Defenses against Pancreatic Cancer Metastasis Cancer Res. (IF 11.2) Pub Date : 2024-02-15 Christine Alewine
Although pancreatic cancer is a systemic disease that metastasizes early in its course, the signaling systems that promote this behavior remain incompletely understood. In this issue of Cancer Research, Luckett and colleagues identify a paracrine signaling pathway between cancer cells and macrophages that promotes pancreatic cancer metastasis. The authors used immunocompetent murine pancreatic cancer
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Mesothelin Secretion by Pancreatic Cancer Cells Co-opts Macrophages and Promotes Metastasis Cancer Res. (IF 11.2) Pub Date : 2024-02-15 Teifion Luckett, Maidinaimu Abudula, Lucy Ireland, Mark Glenn, Gaia Bellomo, Ruth Stafferton, Chris Halloran, Paula Ghaneh, Rob Jones, Michael C. Schmid, Ainhoa Mielgo
Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease, yet effective treatments to inhibit PDAC metastasis are lacking. The rich PDAC tumor microenvironment plays a major role in disease progression. Macrophages are the most abundant immune cell population in PDAC tumors and can acquire a range of functions that either hinder or promote tumor growth and metastasis. Here, we identified
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Analysis of tumor-associated AXIN1 missense mutations identifies variants that activate β-catenin signaling Cancer Res. (IF 11.2) Pub Date : 2024-02-15 Ruyi Zhang, Shanshan Li, Kelly Schippers, Yunlong Li, Boaz Eimers, Marla Lavrijsen, Ling Wang, Guofei Cui, Xin Chen, Maikel P. Peppelenbosch, Joyce H.G. Lebbink, Ron Smits
AXIN1 is a major component of the β-catenin destruction complex and is frequently mutated in various cancer types, particularly liver cancers. Truncating AXIN1 mutations are recognized to encode a defective protein that leads to β-catenin stabilization, but the functional consequences of missense mutations are not well characterized. Here, we first identified the GSK3β, β-catenin and RGS/APC interaction
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ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts Cancer Res. (IF 11.2) Pub Date : 2024-02-15 Bomiao Hu, Marc Wiesehöfer, Fernando J. de Miguel, Zongzhi Liu, Lok-Hei Chan, Jungmin Choi, Mary Ann Melnick, Anna Arnal-Estape, Zenta Walther, Dejian Zhao, Francesc Lopez-Giraldez, Anna Wurtz, Guoping Cai, Rong Fan, Scott Gettinger, Andrew Xiao, Qin Yan, Robert Homer, Don X. Nguyen, Katerina Politi
The majority of EGFR mutant lung adenocarcinomas respond well to EGFR tyrosine kinase inhibitors (TKIs). However, most of these responses are partial with drug tolerant residual disease remaining even at the time of maximal response. This residual disease can ultimately lead to relapses, which eventually develop in most patients. To investigate the cellular and molecular properties of residual tumor
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A Cluster of Evolutionarily Recent KRAB Zinc Finger Proteins Protects Cancer Cells from Replicative Stress–Induced Inflammation Cancer Res. (IF 11.2) Pub Date : 2024-02-12 Filipe Martins, Olga Rosspopoff, Joana Carlevaro-Fita, Romain Forey, Sandra Offner, Evarist Planet, Cyril Pulver, HuiSong Pak, Florian Huber, Justine Michaux, Michal Bassani-Sternberg, Priscilla Turelli, Didier Trono
Heterochromatin loss and genetic instability enhance cancer progression by favoring clonal diversity, yet uncontrolled replicative stress leads to mitotic catastrophe and inflammatory responses that promote immune rejection. KRAB domain-containing zinc finger proteins (KZFP) contribute to heterochromatin maintenance at transposable elements (TE). Here, we identified an association of upregulation of
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Single-cell analysis identifies NOTCH3-mediated interactions between stromal cells that promote microenvironment remodeling and invasion in lung adenocarcinoma Cancer Res. (IF 11.2) Pub Date : 2024-02-09 Handan Xiang, Yidan Pan, Marc A. Sze, Marta Wlodarska, Ling Li, Karyn Ann. Van De Mark, Haleema Qamar, Casey J. Moure, Douglas E. Linn, Josephine Hai, Ying Huo, James Clarke, Tze Guan Tan, Samantha Ho, Karen W. Teng, Muhammad Nadzim. Ramli, Michael Nebozhyn, Chunsheng Zhang, Julianne Barlow, Corinne E. Gustafson, Savanna Gornisiewicz, Thomas P. Albertson, Stephanie L. Korle, Raphael Bueno, Lily Y.
Cancer immunotherapy has revolutionized the treatment of lung adenocarcinoma (LUAD); however, a significant proportion of patients do not respond. Recent transcriptomic studies to understand determinants of immunotherapy response have pinpointed stromal-mediated resistance mechanisms. To gain a better understanding of stromal biology at the cellular and molecular level in LUAD, we performed single-cell
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Sarcoma cells secrete hypoxia-modified collagen VI to weaken the lung endothelial barrier and promote metastasis Cancer Res. (IF 11.2) Pub Date : 2024-02-09 Ying Liu, Ileana Murazzi, Ashley M. Fuller, Hehai Pan, Valerie M. Irizarry-Negron, Ann DeVine, Rohan Katti, Nicolas Skuli, Gabrielle E. Ciotti, Koreana Pak, Michael A. Pack, M. Celeste Simon, Kristy Weber, Kumarasen Cooper, T.S. Karin Eisinger-Mathason
Intratumoral hypoxia correlates with metastasis and poor survival in sarcoma patients. Using an impedance sensing assay and a zebrafish intravital microinjection model, we demonstrated here that the hypoxia-inducible collagen-modifying enzyme lysyl hydroxylase PLOD2 and its substrate collagen type VI (COLVI) weaken the lung endothelial barrier and promote transendothelial migration. Mechanistically
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Chromoplexy is a frequent early clonal event in EWSR1-rearranged round cell sarcomas that can be detected using clinically validated targeted sequencing panels Cancer Res. (IF 11.2) Pub Date : 2024-02-09 Josephine K. Dermawan, Emily Slotkin, William D. Tap, Paul Meyers, Leonard Wexler, John Healey, Fabio Vanoli, Chad M. Vanderbilt, Cristina R. Antonescu
Chromoplexy is a phenomenon defined by large-scale chromosomal chained rearrangements. A previous study observed chromoplectic events in a subset of Ewing sarcomas (ES), which was linked to an increased relapse rate. Chromoplexy analysis could potentially facilitate patient risk stratification, particularly if it could be detected with clinically applied targeted next-generation sequencing (NGS) panels
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Adding new dimensions to 3D cancer models Cancer Res. (IF 11.2) Pub Date : 2024-02-09 Kevan Chu, Lukas E. Dow
Understanding patient-specific responses to anti-cancer therapies and how individual tumors interact with their tumor microenvironment (TME) is a challenging task. To measure the impact of the TME on diverse and clinically-relevant treatments, Zapatero, Tong, and colleagues coupled patient-derived organoid (PDO) and cancer-associated fibroblast (CAF) co-cultures with high-throughput mass cytometry-based
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Breast Cancer Stem Cells Secrete MIF to Mediate Tumor Metabolic Reprogramming that Drives Immune Evasion Cancer Res. (IF 11.2) Pub Date : 2024-02-09 Linlin Yan, Mingming Wu, Tianyu Wang, Hui Yuan, Xiao Zhang, Huafeng Zhang, Tao Li, Vijay Pandey, Xinghua Han, Peter E. Lobie, Tao Zhu
Reprogramming of energy metabolism exerts pivotal functions in cancer progression and immune surveillance. Identification of the mechanisms mediating metabolic changes in cancer may lead to improved strategies to suppress tumor growth and stimulate anti-tumor immunity. Here, it was observed that the secretomes of hypoxic breast cancer cells and breast cancer stem cells (BCSCs) induced reprogramming
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Th17 cells secrete TWEAK to trigger epithelial-mesenchymal transition and promote colorectal cancer liver metastasis Cancer Res. (IF 11.2) Pub Date : 2024-02-09 Xin Liu, Xin Wang, Qingxia yang, Li Luo, Ziqin Liu, Xiaoxue Ren, Kai Lei, Shangru Li, Zonglin Xie, Gaomin Zheng, Yifan Zhang, Yijie Hao, Qianying Zhou, Yingdong Hou, Fei Fang, Wu Song, Ji Cui, Jinping Ma, Wenxuan Xie, Shunli Shen, Ce Tang, Sui Peng, Jun Yu, Ming Kuang, Xinming Song, Fang Wang, Lixia Xu
Liver metastasis is the leading cause of mortality in patients with colorectal cancer (CRC). Given the significance of both epithelial-mesenchymal transition (EMT) of tumor cells and the immune microenvironment in CRC liver metastasis (CRLM), the interplay between them could hold the key for developing improved treatment options. We employed multi-omics analysis of 130 samples from 18 synchronous CRLM
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Targeting TACC3 induces immunogenic cell death and enhances T-DM1 response in HER2-positive breast cancer Cancer Res. (IF 11.2) Pub Date : 2024-02-08 Mustafa Emre Gedik, Ozge Saatci, Nathaniel Oberholtzer, Meral Uner, Ozge Akbulut-Caliskan, Metin Cetin, Mertkaya Aras, Kubra Ibis, Burcu Caliskan, Erden Banoglu, Stefan Wiemann, Ayşegül Üner, Sercan Aksoy, Shikhar Mehrotra, Ozgur Sahin
Trastuzumab emtansine (T-DM1) was the first and one of the most successful antibody-drug conjugates (ADCs) approved for treating refractory HER2-positive breast cancer. Despite its initial clinical efficacy, resistance is unfortunately common, necessitating approaches to improve response. Here, we found that in sensitive cells T-DM1 induced spindle assembly checkpoint (SAC)-dependent immunogenic cell
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A metabolic-epigenetic mechanism directs cell fate and therapeutic sensitivity in breast cancer Cancer Res. (IF 11.2) Pub Date : 2024-02-08 Matthew J. Bernard, Andrew S. Goldstein
Over the past decade, studies have increasingly shed light on a reciprocal relationship between cellular metabolism and cell fate, meaning that a cell’s lineage both drives and is governed by its specific metabolic features. A recent study by Zhang and colleagues, published in Cell Metabolism, describes a novel metabolic-epigenetic regulatory axis that governs lineage identity in triple negative breast
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Fibroblasts in the aged pancreas drive pancreatic cancer progression Cancer Res. (IF 11.2) Pub Date : 2024-02-08 Daniel J. Zabransky, Yash Chhabra, Mitchell E. Fane, Emma Kartalia, James M. Leatherman, Laura Hüser, Jacquelyn W. Zimmerman, Daniel Delitto, Song Han, Todd D. Armstrong, Soren Charmsaz, Samantha Guinn, Sneha Pramod, Elizabeth D. Thompson, Steven J. Hughes, Jennifer O'Connell, Josephine M. Egan, Elizabeth M. Jaffee, Ashani T. Weeraratna
Pancreatic cancer is more prevalent in older individuals and often carries a poorer prognosis for them. The relationship between the microenvironment and pancreatic cancer is multifactorial, and age-related changes in non-malignant cells in the tumor microenvironment may play a key role in promoting cancer aggressiveness. Since fibroblasts have profound impacts on pancreatic cancer progression, we
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Integrated Proteogenomics Uncover Mechanisms of Glioblastoma Evolution, Pointing to Novel Therapeutic Targets. Cancer Res. (IF 11.2) Pub Date : 2024-02-08 Jiabo Li, Ling-kai Shih, Daniel J. Brat
Nearly all glioblastoma (GBM) patients relapse following standard treatment and eventually succumb to disease. While large scale, integrated multi-omic studies have tremendously advanced the understanding of primary GBM at the cellular and molecular level, the post-therapeutic trajectory and biological properties of recurrent GBM remain poorly understood. This knowledge gap was addressed in a recent
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Immunometabolic adaptation of CD19-targeted CAR T cells in the central nervous system microenvironment of patients promotes memory development Cancer Res. (IF 11.2) Pub Date : 2024-02-05 Lior Goldberg, Eric R. Haas, Ryan Urak, Vibhuti Vyas, Khyatiben V. Pathak, Krystine Garcia-Mansfield, Patrick Pirrotte, Jyotsana Singhal, James L. Figarola, Ibrahim Aldoss, Stephen J. Forman, Xiuli Wang
Metabolic reprogramming is a hallmark of T cell activation, and metabolic fitness is fundamental for T cell-mediated anti-tumor immunity. Insights into the metabolic plasticity of chimeric antigen receptor (CAR) T cells in patients could help identify approaches to improve their efficacy in treating cancer. Here, we investigated the spatiotemporal immunometabolic adaptation of CD19-targeted CAR T cells
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Integrating AI-powered digital pathology and imaging mass cytometry identifies key classifiers of tumor cells, stroma, and immune cells in non-small cell lung cancer Cancer Res. (IF 11.2) Pub Date : 2024-02-05 Alessandra Rigamonti, Marika Viatore, Rebecca Polidori, Daoud Rahal, Marco Erreni, Maria Rita. Fumagalli, Damiano Zanini, Andrea Doni, Anna Rita. Putignano, Paola Bossi, Emanuele Voulaz, Marco Alloisio, Sabrina Rossi, Paolo Andrea. Zucali, Armando Santoro, Vittoria Balzano, Paola Nisticò, Friedrich Feuerhake, Alberto Mantovani, Massimo Locati, Federica Marchesi
Artificial intelligence (AI)-powered approaches are becoming increasingly used as histopathological tools to extract sub-visual features and improve diagnostic workflows. On the other hand, hi-plex approaches are widely adopted to analyze the immune ecosystem in tumor specimens. Here, we aimed at combining AI-aided histopathology and imaging mass cytometry (IMC) to analyze the ecosystem of non-small
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The web-based portal SpatialTME integrates histological images with single-cell and spatial transcriptomics to explore the tumor microenvironment Cancer Res. (IF 11.2) Pub Date : 2024-02-05 Jintong Shi, Xia Wei, Zhenzhen Xun, Xinyu Ding, Yao Liu, Lianxin Liu, Youqiong Ye
The tumor microenvironment (TME) represents a complex network in which tumor cells communicate not only with each other but also with stromal and immune cells. The intercellular interactions in the TME contribute to tumor initiation, progression, metastasis, and treatment outcome. Recent advances in spatial transcriptomics (ST) have revolutionized the molecular understanding of the TME at the spatial
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The extracellular niche and tumor microenvironment enhance KRAS inhibitor efficacy in pancreatic cancer. Cancer Res. (IF 11.2) Pub Date : 2024-01-31 Vishnu Kumarasamy, Jianxin Wang, Costakis Frangou, Yin Wan, Andrew Dynka, Hanna Rosenheck, Prasenjit Dey, Ethan V. Abel, Erik S. Knudsen, Agnieszka K. Witkiewicz
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that lacks effective treatment options, highlighting the need for developing new therapeutic interventions. Here, we assessed the response to pharmacological inhibition of KRAS, the central oncogenic driver of PDAC. In a panel of PDAC cell lines, inhibition of KRASG12D with MRTX1133 yielded variable efficacy in suppressing cell growth
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Osteosarcoma cells secrete CXCL14 that activates integrin α11β1 on fibroblasts to form a lung metastatic niche Cancer Res. (IF 11.2) Pub Date : 2024-01-31 Yanyang Xu, Chuangzhong Deng, Hongmin Chen, YiJiang Song, Huaiyuan Xu, Guohui Song, Xinliang Wang, Tianqi Luo, Weiqing Chen, Jiahui Ma, Anyu Zeng, Shujing Huang, Zhihao Chen, Jianchang Fu, Ming Gong, Yi Tai, Anfei Huang, Huixiong Feng, Jinxin Hu, Xiaojun Zhu, Qinglian Tang, Jinchang Lu, Jin Wang
Cooperation between primary malignant cells and stromal cells can mediate the establishment of lung metastatic niches. Here, we characterized the landscape of cell populations in the tumor microenvironment in treatment-naïve osteosarcoma using single cell RNA-sequencing and identified a stem cell-like cluster with tumor cell-initiating properties and pro-metastatic traits. CXCL14 was specifically enriched
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Cytidine deaminase resolves replicative stress and protects pancreatic cancer from DNA-targeting drugs Cancer Res. (IF 11.2) Pub Date : 2024-01-31 Audrey Lumeau, Nicolas Bery, Audrey Frances, Marion Gayral, Guillaume Labrousse, Cyril Ribeyre, Charlène Lopez, Adèle Nevot, Abdessamad El Kaoutari, Naima Hanoun, Emeline Sarot, Marion Perrier, Frédéric Pont, Juan Pablo Cerapio, Jean-Jacques Fournié, Frédéric Lopez, Miguel Madrid-Mencia, Vera Pancaldi, Marie-Jeanne Pillaire, Valérie Bergoglio, Jerome Torrisani, Nelson Dusetti, Jean-Sébastien Hoffmann
Cytidine deaminase (CDA) functions in the pyrimidine salvage pathway for DNA and RNA synthesis and has been shown to protect cancer cells from deoxycytidine-based chemotherapies. In this study, we observed that CDA was overexpressed in pancreatic adenocarcinoma from patients at baseline and was essential for experimental tumor growth. Mechanistic investigations revealed that CDA localized to replication
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Lactate utilization enables metabolic escape to confer resistance to BET inhibition in acute myeloid leukemia Cancer Res. (IF 11.2) Pub Date : 2024-01-29 Andrew J. Monteith, Haley E. Ramsey, Alexander J. Silver, Donovan Brown, Dalton Greenwood, Brianna N. Smith, Ashley D. Wise, Juan Liu, Sarah D. Olmstead, Jackson Watke, Maria P. Arrate, Agnieszka E. Gorska, Londa Fuller, Jason W. Locasale, Matthew C. Stubbs, Jeffrey C. Rathmell, Michael R. Savona
Impairing the BET-family co-activator BRD4 with small molecule inhibitors (BETi) showed encouraging pre-clinical activity in treating acute myeloid leukemia (AML). However, dose-limiting toxicities and limited clinical activity dampened the enthusiasm for BETi as a single agent. BETi resistance in AML myeloblasts was found to correlate with maintaining mitochondrial respiration, suggesting that identifying
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KDM5C-mediated recruitment of BRD4 to chromatin regulates enhancer activation and BET inhibitor sensitivity Cancer Res. (IF 11.2) Pub Date : 2024-01-29 Yulong Qiang, Jiachen Fan, Chuanshuai Xie, Leilei Yan, Xiaofei Song, Nan Zhang, Yan Lin, jie xiong, Wei Zhang, Yu Liu, Lei Wei, Yu Li, Shizhen Chen, Kaiwei Liang, Feng Li
The BET family member BRD4 is a bromodomain-containing protein that plays a vital role in driving oncogene expression. Given their pivotal role in regulating oncogenic networks in various cancer types, BET inhibitors (BETis) have been developed, but the clinical application has been impeded by dose-limiting toxicity and resistance. Understanding the mechanisms of BRD4 activity and identifying predictive
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Tumor cell-intrinsic p38 MAPK signaling promotes IL1⍺-mediated stromal inflammation and therapeutic resistance in pancreatic cancer Cancer Res. (IF 11.2) Pub Date : 2024-01-29 Samara P. Singh, Austin R. Dosch, Siddharth Mehra, Iago De Castro Silva, Anna Bianchi, Vanessa T. Garrido, Zhiqun Zhou, Andrew Adams, Haleh Amirian, Edmond W. Box, Xiaodian Sun, Yuguang Ban, Jashodeep Datta, Nagaraj S. Nagathihalli, Nipun B. Merchant
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a KRAS-driven inflammatory program and a desmoplastic stroma, which contribute to the profoundly chemoresistant phenotype. The tumor stroma contains an abundance of cancer-associated fibroblasts (CAFs), which engage in extensive paracrine crosstalk with tumor cells to perpetuate pro-tumorigenic inflammation. Interleukin-1α (IL1α), a pleiotropic
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Gut microbiome mediates ferroptosis resistance for colorectal cancer development Cancer Res. (IF 11.2) Pub Date : 2024-01-26 Ruoxi Zhang, Rui Kang, Daolin Tang
Colorectal cancer (CRC) is a prevalent cancer type in the United States, affecting both genders and influenced by genetics and environmental factors. The role of the gut microbiome in CRC development and therapy response is a burgeoning field of study. A recent study uncovered that trans-3-indoleacrylic acid (IDA), a microbial metabolite from P. anaerobius, promotes CRC by inhibiting ferroptosis, a
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Co-targeting CDK4/6 and BRD4 promotes senescence and ferroptosis sensitivity in cancer Cancer Res. (IF 11.2) Pub Date : 2024-01-26 Xianbing Zhu, Zheng Fu, Kendall Dutchak, Azadeh Arabzadeh, Simon Milette, Jutta Steinberger, Geneviève Morin, Anie Monast, Virginie Pilon, Tim Kong, Bianca N. Adams, Erika Prando Munhoz, Hannah JB. Hosein, Tianxu Fang, Jing Su, Yibo Xue, Roni Rayes, Veena Sangwan, Logan A. Walsh, Guojun Chen, Daniela F. Quail, Jonathan D. Spicer, Morag Park, David Dankort, Sidong Huang
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for breast cancer treatment and show activity against other malignancies, including KRAS-mutant non-small cell lung cancer (NSCLC). However, the clinical efficacy of CDK4/6 inhibitors is limited due to frequent drug resistance and their largely cytostatic effects. Through a genome-wide cDNA screen, we identified that bromodomain-containing
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Subclonal Cancer Driver Mutations are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas Cancer Res. (IF 11.2) Pub Date : 2024-01-25 Hunter R. Underhill, Michael Karsy, Christian J. Davidson, Sabine Hellwig, Samuel Stevenson, Eric A. Goold, Sydney Vincenti, Drew L. Sellers, Charlie Dean, Brion E. Harrison, Mary P. Bronner, Howard Colman, Randy L. Jensen
Adult diffuse gliomas commonly recur regardless of therapy. As recurrence typically arises from the peritumoral edema adjacent to the resected bulk tumor, the profiling of somatic mutations from infiltrative malignant cells within this critical, unresected region could provide important insights into residual disease. A key obstacle has been the inability to distinguish between next-generation sequencing
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Human tumor-associated macrophages and neutrophils regulate anti-tumor antibody efficacy through lethal and sublethal trogocytosis Cancer Res. (IF 11.2) Pub Date : 2024-01-25 Sunil Singhal, Abhishek S. Rao, Jason Stadanlick, Kyle Bruns, Neil T. Sullivan, Andres Bermudez, Adam Honig-Frand, Ryan Krouse, Sachinthani Arambepola, Emily Guo, Edmund K. Moon, George Georgiou, Thomas Valerius, Steven M. Albelda, Evgeniy B. Eruslanov
The clinical benefits of tumor-targeting antibodies (tAbs) are modest in solid human tumors. The efficacy of many tAbs is dependent on Fc Receptor (FcR)-expressing leukocytes that bind Fc fragments of tAb. Tumor-associated macrophages (TAM) and neutrophils (TAN) represent the majority of FcR+ effectors in solid tumors. A better understanding of the mechanisms by which TAM and TAN regulate tAb response
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TFE3-splicing factor fusions represent functional drivers and druggable targets in translocation renal cell carcinoma Cancer Res. (IF 11.2) Pub Date : 2024-01-24 Nur P. Damayanti, Ricardo A. Cordova, Christopher Rupert, Ilaria Delle Fontane, Li Shen, Sabrina Orsi, Angela J. Klunk, W. Marston Linehan, Kirk A. Staschke, Peter C. Hollenhorst, David E. Heppner, Roberto Pili
TFE3 is a member of the basic helix-loop-helix leucine zipper MiT transcription factor family, and its chimeric proteins are associated with translocation renal cell carcinoma (tRCC). Despite the variety of gene fusions, most TFE3 fusion partner genes are related to spliceosome machinery. Dissecting the function of TFE3 fused to spliceosome machinery factors (TFE3-SF) could direct the development of
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Chromatin Remodelers Are Regulators of the Tumor Immune Microenvironment Cancer Res. (IF 11.2) Pub Date : 2024-01-24 Apoorvi Chaudhri, Gregory Lizee, Patrick Hwu, Kunal Rai
Immune checkpoint inhibitors show remarkable responses in a wide range of cancers, yet patients develop adaptive resistance. This necessitates the identification of alternate therapies that synergize with immunotherapies. Epigenetic modifiers are potent mediators of tumor intrinsic mechanisms and have been shown to regulate immune response genes, making them prime targets for therapeutic combinations
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The imipridone ONC213 targets α-ketoglutarate dehydrogenase to induce mitochondrial stress and suppress oxidative phosphorylation in acute myeloid leukemia Cancer Res. (IF 11.2) Pub Date : 2024-01-24 Yongwei Su, Jenna L. Carter, Xinyu Li, Yu Fukuda, Ashley Gray, John Lynch, Holly Edwards, Jun Ma, Patrick Schreiner, Lisa Polin, Juiwanna Kushner, Sijana H. Dzinic, Steven A. Buck, Shondra M. Pruett-Miller, Katie Hege. Hurrish, Camenzind Robinson, Xinan Qiao, Shuang Liu, Shuangshuang Wu, Guan Wang, Jing Li, Joshua E. Allen, Varun V. Prabhu, Aaron D. Schimmer, Dhananjay Joshi, Shiva Kalhor-Monfared
Eradication of acute myeloid leukemia (AML) is therapeutically challenging; many patients succumb to AML despite initially responding to conventional treatments. Here, we showed that the imipridone ONC213 elicits potent antileukemia activity in a subset of AML cell lines and primary patient samples, particularly in leukemia stem cells, while producing negligible toxicity in normal hematopoietic cells
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Nutrient sensing in macrophages linked to reorganized tumor vasculature Cancer Res. (IF 11.2) Pub Date : 2024-01-19 Hilda L. Chan, Xiang H.-F. Zhang
Macrophages are plastic immune cells that have varying functions dependent on stimulation from their environment. In a recent issue of Immunity, Do and colleagues demonstrated that activating mechanistic target of rapamycin complex 1 signaling in tumor macrophages alters their metabolism, localization, and function. Specifically, these tumor macrophages promote vascular remodeling that develops a hypoxic
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N6-methyladenosine reader YTHDF1 promotes stemness and therapeutic resistance in hepatocellular carcinoma by enhancing NOTCH1 expression Cancer Res. (IF 11.2) Pub Date : 2024-01-19 Xinyue Zhang, Tianhong Su, Yifan Wu, Yuhong Cai, Lina Wang, Cong Liang, Lei Zhou, Shiyan Wang, Xiao-Xing Li, Sui Peng, Ming Kuang, Jun Yu, Lixia Xu
N6-methyladenosine (m6A) RNA modification is the most common and conserved epigenetic modification in mRNA and has been shown to play important roles in cancer biology. As the m6A reader YTHDF1 has been reported to promote progression of hepatocellular carcinoma (HCC), it represents a potential therapeutic target. In this study, we evaluated the clinical significance of YTHDF1 using human HCC samples
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AKT1 interacts with DHX9 to mitigate R-loop-induced replication stress in ovarian cancer Cancer Res. (IF 11.2) Pub Date : 2024-01-19 Tzu-Ting Huang, Chih-Yuan Chiang, Jayakumar R. Nair, Kelli M. Wilson, Ken Cheng, Jung-Min Lee
PARP inhibitor (PARPi)-resistant BRCA mutant (BRCAm) high-grade serous ovarian cancer (HGSOC) represents a new clinical challenge with unmet therapeutic needs. Here, we performed a quantitative high-throughput drug combination screen that identified the combination of an ATR inhibitor (ATRi) and an AKT inhibitor (AKTi) as an effective treatment strategy for both PARPi-sensitive and PARPi-resistant
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Cyclic fasting-mimicking diet plus bortezomib and rituximab is an effective treatment for chronic lymphocytic leukemia Cancer Res. (IF 11.2) Pub Date : 2024-01-19 Franca Raucci, Claudio Vernieri, Maira Di Tano, Francesca Ligorio, Olga Blaževitš, Samuel Lazzeri, Anastasiya Shmahala, Giuseppe Fragale, Giulia Salvadori, Gabriele Varano, Stefano Casola, Roberta Buono, Euplio Visco, Filippo de Braud, Valter D. Longo
Cyclic fasting-mimicking diet (FMD) is an experimental nutritional intervention with potent antitumor activity in preclinical models of solid malignancies. FMD cycles are also safe and active metabolically and immunologically in cancer patients. Here, we reported on the outcome of FMD cycles in two chronic lymphocytic leukemia (CLL) patients and investigated the effects of fasting and FMD cycles in
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Targeting the epigenetic reader ENL inhibits super-enhancer-driven oncogenic transcription and synergizes with BET inhibition to suppress tumor progression Cancer Res. (IF 11.2) Pub Date : 2024-01-19 Yongheng Chen, Ying Ying, Wenlong Ma, Hongchao Ma, Liang Shi, Xuefeng Gao, Min Jia, Meiqi Li, Xiaoman Song, Weixiao Kong, Wei Chen, Xiangyi Zheng, Tobias Achu Muluh, Xiaobin Wang, Maolin Wang, Xing-sheng Shu
Epigenetic alterations at cis-regulatory elements (CREs) fine-tune transcriptional output. Epigenetic readers interact with CREs and can cooperate with other chromatin regulators to drive oncogene transcription. Here, we found that the YEATS domain-containing histone acetylation reader ENL (eleven-nineteen leukemia) acts as a key regulator of super-enhancers (SEs), which are highly active distal CREs