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Human 3D ovarian cancer models reveal malignant cell intrinsic and extrinsic factors that influence CAR T cell activity Cancer Res. (IF 11.2) Pub Date : 2024-05-31 Joash D. Joy, Beatrice Malacrida, Florian Laforets, Panoraia Kotantaki, Eleni Maniati, Ranjit Manchanda, Alessandro Annibaldi, Sarah Hopkins, Ianire Garrobo-Calleja, Julien Gautrot, Frances R. Balkwill
In vitro preclinical testing of chimeric antigen receptor (CAR) T cells is mostly carried out in monolayer cell cultures. However, alternative strategies are needed to take into account the complexity and the effects of the tumor microenvironment (TME). Here, we describe the modulation of CAR T cell activity by malignant cells and fibroblasts in human 3D in vitro cell models of increasing complexity
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VPAC2 Receptor Signaling Promotes Growth and Immunosuppression in Pancreatic Cancer Cancer Res. (IF 11.2) Pub Date : 2024-05-29 Tenzin Passang, Shuhua Wang, Hanwen Zhang, Fanyuan Zeng, Po-Chih Hsu, Wenxi Wang, Jian-Ming Li, Yuan Liu, Sruthi Ravindranathan, Gregory B. Lesinski, Edmund K. Waller
Pancreatic cancer (PDAC) harbors a complex tumor microenvironment (TME), and crosstalk between cells in the TME can contribute to drug resistance and relapse. Vasoactive intestinal peptide (VIP) is overexpressed in PDAC, and VIP receptors expressed on T cells are a targetable pathway that sensitizes PDAC to immunotherapy. In this study, we showed that pancreatic cancer cells engage in autocrine VIP
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Physical Activity Decreases Inflammation and Delays Development of Obesity-Associated Pancreatic Ductal Adenocarcinoma Cancer Res. (IF 11.2) Pub Date : 2024-05-23 Valentina Pita-Grisanti, Ericka Vélez-Bonet, Kaylin Chasser, Zachary Hurst, Alexus Liette, Grace Vulic, Kelly Dubay, Ali Lahooti, Niharika Badi, Olivia Ueltschi, Kristyn Gumpper-Fedus, Hsiang-Yin Hsueh, Ila Lahooti, Myrriah Chavez-Tomar, Samantha Terhorst, Sue E. Knoblaugh, Lei Cao, Wei Huang, Christopher C. Coss, Thomas A. Mace, Fouad Choueiry, Alice Hinton, Stacey Culp, Jennifer M. Mitchell, Rosemarie
Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), a deadly disease with limited preventive strategies. Lifestyle interventions to decrease obesity represent a potential approach to prevent obesity-associated PDAC. Here, we examined whether decreasing obesity through physical activity (PA) and/or dietary changes could decrease inflammation in humans and prevent obesity-associated
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Targeting Super-Enhancer-Driven Transcriptional Dependencies Suppresses Aberrant Hedgehog Pathway Activation and Overcomes Smoothened Inhibitor Resistance Cancer Res. (IF 11.2) Pub Date : 2024-05-22 Yi Sui, Teng Wang, Yanqing Mei, Ying Zhu, Wenyan Jiang, Jiayi Shen, Siyuan Yan, Wenjie Lu, Kewen Zhao, Jialin Mo, Chaochen Wang, Yujie Tang
Aberrant activation of the Hedgehog (Hh) signaling pathway plays important roles in oncogenesis and therapeutic resistance in several types of cancer. The clinical application of FDA-approved Hh-targeted Smoothened inhibitors (SMOi) is hindered by the emergence of primary or acquired drug resistance. Epigenetic and transcriptional targeted therapies represent a promising direction for developing improved
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FBXO32 Stimulates Protein Synthesis to Drive Pancreatic Cancer Progression and Metastasis Cancer Res. (IF 11.2) Pub Date : 2024-05-22 Dan Su, Ruobing Wang, Guangyu Chen, Chen Ding, Yueze Liu, JInxin Tao, Yuanyang Wang, Jiangdong Qiu, Wenhao Luo, Guihu Weng, Yang Gang, Taiping Zhang
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide, primarily due to its rapid progression. The current treatment options for PDAC are limited, and a better understanding of the underlying mechanisms responsible for PDAC progression is required to identify improved therapeutic strategies. Here, we identified FBXO32 as an oncogenic driver in PDAC.
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Large-scale alternative polyadenylation-wide association studies to identify putative cancer susceptibility genes Cancer Res. (IF 11.2) Pub Date : 2024-05-17 Xingyi Guo, Jie Ping, Yaohua Yang, Xinwan Su, Xiao-Ou Shu, Wanqing Wen, Zhishan Chen, Yunjing Zhang, Ran Tao, Guochong Jia, Jingni He, Qiuyin Cai, Qingrun Zhang, Graham G. Giles, Rachel Pearlman, Gad Rennert, Pavel Vodicka, Amanda Phipps, Stephen B. Gruber, Graham Casey, Ulrike Peters, Jirong Long, Weiqiang Lin, Wei Zheng
Alternative polyadenylation (APA) modulates mRNA processing in the 3’ untranslated regions (3’ UTR), affecting mRNA stability and translation efficiency. Research into genetically regulated APA has the potential to provide insights into cancer risk. Herein, we conducted large alternative polyadenylation-wide association studies (APA-WAS) to investigate associations of APA levels with cancer risk. Genetic
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Allysine-Targeted Molecular MRI Enables Early Prediction of Chemotherapy Response in Pancreatic Cancer Cancer Res. (IF 11.2) Pub Date : 2024-05-17 Hua Ma, Shadi A. Esfahani, Shriya Krishna, Bahar Ataeinia, Iris Y. Zhou, Nicholas J. Rotile, Jonah Weigand-Whittier, Avery T. Boice, Andrew S. Liss, Kenneth K. Tanabe, Peter Caravan
Neoadjuvant therapy (NAT) is routinely used in pancreatic ductal adenocarcinoma (PDAC), but not all tumors respond to this treatment. Current clinical imaging techniques are not able to precisely evaluate and predict the response to neoadjuvant therapies over several weeks. A strong fibrotic reaction is a hallmark of a positive response, and during fibrogenesis allysine residues are formed on collagen
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Striking the Balance with a PD-L1×4–1BB Bispecific Antibody Cancer Res. (IF 11.2) Pub Date : 2024-05-15 JongHoon Ha, Adam J. Grippin, Betty Y.S. Kim, Wen Jiang
Antibody-based immune checkpoint blockade therapy has revolutionized the field of cancer immunotherapy, yet its efficacy remains limited in immunologically cold tumors. Combining checkpoint inhibitors with costimulatory agonists improves tumoricidal activity of T cells but also can lead to off-target hepatotoxicity. Although bispecific antibodies confer tumor selectivity to alleviate undesirable adverse
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Overcoming Nutrient Stress: Integrin αvβ3-Driven Metabolic Adaptation Supports Tumor Initiation Cancer Res. (IF 11.2) Pub Date : 2024-05-15 Elena Rainero
Nutrient stress accompanies several stages of tumor progression, including metastasis formation. Metabolic reprogramming is a hallmark of cancer, and it has been associated with stress tolerance and anchorage-independent cell survival. Adaptive responses are required to support cancer cell survival under these conditions. In this issue of Cancer Research, Nam and colleagues showed that the extracellular
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HiChIP-based Epigenomic Footprinting Identifies a Promoter Variant of UXS1 that Confers Genetic Susceptibility to Gastroesophageal Cancer. Cancer Res. (IF 11.2) Pub Date : 2024-05-15 Ansley Gnanapragasam, Eftyhios Kirbizakis, Anna Li, Kyle H. White, Katelyn L. Mortenson, Juliana Cavalcante de Moura, Wajih Jawhar, Yifei Yan, Reilly Falter, Colleen Russett, Betty Giannias, Sophie Camilleri-Broët, Nicholas Bertos, Jonathan Cools-Lartigue, Livia Garzia, Veena Sangwan, Lorenzo E. Ferri, Xiaoyang Zhang, Swneke D. Bailey
Genome-wide association studies (GWAS) have identified more than a hundred single nucleotide variants (SNVs) associated with the risk of gastroesophageal cancer (GEC). The majority of the identified SNVs map to noncoding regions of the genome. Uncovering the causal SNVs and the genes they modulate could help improve GEC prevention and treatment. Here, we used HiChIP against histone 3 lysine 27 acetylation
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The DRAP1/DR1 Repressor Complex Increases mTOR Activity to Promote Progression and Confer Everolimus Sensitivity in Triple-Negative Breast Cancer Cancer Res. (IF 11.2) Pub Date : 2024-05-15 Min-Ying Huang, Shu-Yuan Hu, Jia Dong, Ling Deng, Lisa Andriani, Xiao-Yan Ma, Yin-Ling Zhang, Fang-Lin Zhang, Zhi-Ming Shao, Da-Qiang Li
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Transcriptional dysregulation is a hallmark of cancer, and several transcriptional regulators have been demonstrated to contribute to cancer progression. Here, we identified upregulation of the transcriptional corepressor DRAP1 in TNBC, which was closely associated with poor recurrence-free survival in TNBC patients
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Estrogen induces LCAT to maintain cholesterol homeostasis and suppress hepatocellular carcinoma development Cancer Res. (IF 11.2) Pub Date : 2024-05-08 Wenzhi He, Min Wang, Xuechun Zhang, Yilan Wang, Dongli Zhao, Wenhua Li, Fang Lei, Min Peng, Zhonglin Zhang, Yufeng Yuan, Zan Huang
Hepatocellular carcinoma (HCC) is an aggressive disease that occurs predominantly in men. Estrogen elicits protective effects against HCC development. Elucidation of the estrogen-regulated biological processes that suppress HCC could lead to improved prevention and treatment strategies. Here, we performed transcriptomic analyses on mouse and human liver cancer and identified LCAT as the most highly
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HDAC Inhibition Increases CXCL12 Secretion to Recruit Natural Killer Cells in Peripheral T Cell Lymphoma Cancer Res. (IF 11.2) Pub Date : 2024-05-08 Jiayan Zhu, Feng Wang, Lining Wang, Bo Dai, Guilin Xu, Luyao Zhao, Huimin Jiang, Wenhui Gao, Tingting Zhang, Chenxi Zhao, Yun-Xuan Li, Jiong Hu, Ke Li
Peripheral T cell lymphoma (PTCL) is a heterogeneous and aggressive disease with a poor prognosis. Histone deacetylase (HDAC) inhibitors have shown inhibitory effects on PTCL. A better understanding of the therapeutic mechanism underlying the effects of HDAC inhibitors could help improve treatment strategies. Here, we found that high expression of HDAC3 is associated with poor prognosis in PTCL. HDAC3
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A Virus-Inspired Inhalable Liponanogel Induces Potent Antitumor Immunity and Regression in Metastatic Lung Tumors Cancer Res. (IF 11.2) Pub Date : 2024-05-08 Junyao Li, Lanqing Luo, Jia He, Jinchao Yu, Xinyan Li, Xueying Shen, Junxia Zhang, Sai Li, Jeffrey M. Karp, Rui Kuai
Pulmonary delivery of immunostimulatory agents such as poly(I:C) to activate double-stranded RNA sensors MDA5 and RIG-I within lung-resident antigen-presenting cells is a potential strategy to enhance antitumor immunity by promoting type I interferon secretion. However, following pulmonary delivery, poly(I:C) suffers from rapid degradation and poor endosomal escape, thus limiting its potency. Inspired
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The Circadian Clock Component RORA Increases Immunosurveillance in Melanoma by Inhibiting PD-L1 Expression Cancer Res. (IF 11.2) Pub Date : 2024-05-08 Dandan Liu, Benliang Wei, Long Liang, Yue Sheng, Shengjie Sun, Xing Sun, Maohua Li, Haobo Li, Chaoying Yang, Yuanliang Peng, Yifang Xie, Chengcai Wen, Lu Chen, Xionghao Liu, Xiang Chen, Hong Liu, Jing Liu
Circadian clock perturbation frequently occurs in cancer and facilitates tumor progression by regulating malignant growth and shaping the immune microenvironment. Emerging evidence has indicated that clock genes are disrupted in melanoma and linked to immune escape. Here, we found that the expression of retinoic acid receptor-related orphan receptor-α (RORA) is downregulated in melanoma patients and
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Single-cell analyses reveal the metabolic heterogeneity and plasticity of the tumor microenvironment during head and neck squamous cell carcinoma progression Cancer Res. (IF 11.2) Pub Date : 2024-05-08 Xiaoyan Meng, Yang Zheng, Lingfang Zhang, Peipei Liu, Zhonglong Liu, Yue He
Metabolic reprogramming is a hallmark of cancer. In addition to metabolic alterations in the tumor cells, multiple other metabolically active cell types in the tumor microenvironment (TME) contribute to the emergence of a tumor-specific metabolic milieu. Here, we defined the metabolic landscape of the TME during progression of head and neck squamous cell carcinoma (HNSCC) by performing single-cell
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Multiplexed Imaging Mass Cytometry Analysis Characterizes the Vascular Niche in Pancreatic Cancer Cancer Res. (IF 11.2) Pub Date : 2024-05-02 Jonathan Sussman, Nathalia Y. Kim, Samantha B. Kemp, Daniel Traum, Takeshi Katsuda, Benjamin M. Kahn, Jason Xu, Il-Kyu Kim, Cody Eskandarian, Devora Delman, Gregory L. Beatty, Klaus H. Kaestner, Amber L. Simpson, Ben Z. Stanger
Oncogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) is driven by complex interactions between the neoplastic component and the tumor microenvironment (TME), which includes immune, stromal, and parenchymal cells. In particular, most PDACs are characterized by a hypovascular and hypoxic environment that alters tumor cell behavior and limits the efficacy of chemotherapy and immunotherapy
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Hold the MYCrophone: MYC Invades Enhancers to Control Cancer Type Gene Programs Cancer Res. (IF 11.2) Pub Date : 2024-05-02 Kevin A. MacPherson-Hawthorne, Rosalie C. Sears
MYC is an oncogenic transcription factor that binds gene promoters to facilitate oncogenic gene expression. When overexpressed, as is the case in most human cancers, MYC also invades active enhancers—cis-regulatory elements that are critical for regulating gene expression. In previous studies, the regulatory significance of MYC enhancer invasion in cancer cells has been debated. In their study published
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Warburg Effect Reshapes Tumor Immunogenicity Cancer Res. (IF 11.2) Pub Date : 2024-04-24 Jose A. Enríquez, María Mittelbrunn
Tumor cells rewire their metabolism to fulfill the demands of highly proliferative cells. This changes cellular metabolism to adapt to fuel and oxygen availability for energy production and to increase the synthesis capacity of building blocks for cell division and growth. In addition, the metabolic shift also modulates the immunogenicity of the tumor cells. Recently, Mahmood and colleagues reported
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Exploring Novel Therapeutic Avenues for Chemotherapy Related Cognitive Impairment Cancer Res. (IF 11.2) Pub Date : 2024-04-24 Jorg Dietrich, Michael W. Parsons, Emiliano Santarnecchi
Many cancer patients are at risk of developing cognitive symptoms that often become evident during or after cancer-directed therapy and may involve difficulties with attention, concentration, multitasking, executive function, and memory. Despite recent advances in identifying potential molecular and cellular mechanisms underlying cancer and chemotherapy-related cognitive impairment, there is generally
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IL1R2 blockade alleviates immunosuppression and potentiates anti-PD-1 efficacy in triple-negative breast cancer Cancer Res. (IF 11.2) Pub Date : 2024-04-24 Jie Xia, Lixing Zhang, Xilei Peng, Juchuanli Tu, Siqin Li, Xueyan He, Fengkai Li, Jiankun Qiang, Haonan Dong, Qiaodan Deng, Cuicui Liu, Jiahui Xu, Rui Zhang, Quentin Liu, Guohong Hu, Chong Liu, Yi-Zhou Jiang, Zhi-Ming Shao, Ceshi Chen, Suling Liu
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. Interleukin-1 receptor type 2 (IL1R2) promotes breast tumor-initiating cell (BTIC) self-renewal and tumor growth in TNBC, indicating that targeting it could improve patient treatment. Here, we observed that IL1R2 blockade strongly attenuated macrophage recruitment and the polarization of
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ACSM1 and ACSM3 regulate fatty acid metabolism to support prostate cancer growth and constrain ferroptosis Cancer Res. (IF 11.2) Pub Date : 2024-04-24 Raj Kumar. Shrestha, Zeyad D. Nassar, Adrienne R. Hanson, Richard Iggo, Scott L. Townley, Jonas Dehairs, Chui Yan Mah, Madison Helm, Mohammadreza Alizadeh-Ghodsi, Marie Pickering, Bart Ghesquiere, Matthew J. Watt, Lake-Ee Quek, Andrew J. Hoy, Wayne D. Tilley, Johannes V. Swinnen, Lisa M. Butler, Luke A. Selth
Solid tumors are highly reliant on lipids for energy, growth, and survival. In prostate cancer, the activity of the androgen receptor (AR) is associated with reprogramming of lipid metabolic processes. Here, we identified acyl-CoA synthetase medium chain family members 1 and 3 (ACSM1 and ACSM3) as AR-regulated mediators of prostate cancer metabolism and growth. ACSM1 and ACSM3 were upregulated in prostate
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Single-Cell and Spatial Transcriptome Profiling Identifies the Transcription Factor BHLHE40 as a Driver of EMT in Metastatic Colorectal Cancer Cancer Res. (IF 11.2) Pub Date : 2024-04-24 Sheng Yang, Dongsheng Zhang, Qingyang Sun, Hongxu Nie, Yue Zhang, Xiaowei Wang, Yuanjian Huang, Yueming Sun
Colorectal cancer (CRC) is one of the most common malignant tumors in humans, with liver metastasis being the primary cause of mortality. The epithelial-mesenchymal transition (EMT) process endows cancer cells with enhanced metastatic potential. To elucidate the cellular mechanisms driving EMT in CRC, we analyzed single-cell RNA-sequencing (scRNA-seq) data from 11 non-metastatic primary tumors (TnM)
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Comprehensive genetic profiling reveals frequent alterations of driver genes on the X chromosome in extranodal NK/T-cell lymphoma Cancer Res. (IF 11.2) Pub Date : 2024-04-24 Yuta Ito, Amira Marouf, Yasunori Kogure, Junji Koya, Raphaël Liévin, Julie Bruneau, Mariko Tabata, Yuki Saito, Sumito Shingaki, Mitsuhiro Yuasa, Kentaro Yamaguchi, Koichi Murakami, Robert Weil, Manon Vavasseur, Guillaume P. Andrieu, Mehdi Latiri, Layla Veleanu, Michaël Dussiot, Isabelle André, Akshay Joshi, Chantal Lagresle-Peyrou, Aude Magerus, Sammara Chaubard, David Lavergne, Emmanuel Bachy, Erika
Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus (EBV)-related neoplasm with male dominance and a poor prognosis. A better understanding of the genetic alterations and their functional roles in ENKTCL could help improve patient stratification and treatments. Here, we performed comprehensive genetic analysis of 177 ENKTCL cases to delineate the landscape of mutations, copy number alterations
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ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs Cancer Res. (IF 11.2) Pub Date : 2024-04-24 Ewa Sicinska, Vijaya Sudhakara Rao Kola, Joseph A. Kerfoot, Madeleine L. Taddei, Alyaa Al-Ibraheemi, Yi-Hsuan Hsieh, Alanna J. Church, Esther Landesman-Bollag, Yosef Landesman, Matthew L. Hemming
Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy driven by the ASPSCR1::TFE3 fusion. A better understanding of the mechanisms by which this oncogenic transcriptional regulator drives cancer growth is needed to help identify potential therapeutic targets. Here, we characterized the transcriptional and chromatin landscapes of ASPS tumors and preclinical models, identifying the essential
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Extracellular vesicles containing circMYBL1 induce CD44 in adenoid cystic carcinoma cells and pulmonary endothelial cells to promote lung metastasis Cancer Res. (IF 11.2) Pub Date : 2024-04-24 Min Fu, Qian Gao, Mian Xiao, Rui-Feng Li, Xin-Yi Sun, Sheng-Lin Li, Xin Peng, Xi-Yuan Ge
Adenoid cystic carcinoma (ACC) is a rare malignant epithelial neoplasm that arises in secretory glands and commonly metastasizes to the lungs. MYBL1 is frequently overexpressed in ACC and has been suggested to be a driver of the disease. Here, we identified a circRNA derived from MYBL1 pre-mRNA that accompanied overexpression of MYBL1 in ACC. Overexpression of circMYBL1 was correlated with increased
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GPR1 and CMKLR1 control lipid metabolism to support development of clear cell renal cell carcinoma Cancer Res. (IF 11.2) Pub Date : 2024-04-19 Dazhi Wang, Iqbal Mahmud, Vijay S. Thakur, Sze Kiat Tan, Daniel G. Isom, David B. Lombard, Mark L. Gonzalgo, Oleksandr N. Kryvenko, Philip L. Lorenzi, Vanina T. Tcheuyap, James Brugarolas, Scott M. Welford
Clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer, is largely incurable in the metastatic setting. ccRCC is characterized by excessive lipid accumulation that protects cells from stress and promotes tumor growth, suggesting that the underlying regulators of lipid storage could represent potential therapeutic targets. Here, we evaluated the regulatory roles of GPR1 and CMKLR1
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CD58 alterations govern antitumor immune responses by inducing PD-L1 and IDO in diffuse large B-cell lymphoma Cancer Res. (IF 11.2) Pub Date : 2024-04-18 Xiyue Xu, Yidan Zhang, Yaxiao Lu, Xiaoyan Zhang, Cuicui Zhao, Jiesong Wang, Qingpei Guan, Yingfang Feng, Meng Gao, Jingwei Yu, Zheng Song, Xia Liu, Zahra Golchehre, Lanfang Li, Weicheng Ren, Qiang Pan-Hammarström, Huilai Zhang, Xianhuo Wang
Recurrent abnormalities in immune surveillance-related genes affect the progression of diffuse large B-cell lymphoma (DLBCL) and modulate the response to therapeutic interventions. CD58 interacts with the CD2 receptor on T cells and natural killer (NK) cells and is recurrently mutated and deleted in DLBCL, suggesting it may play a role in regulating antitumor immunity. Herein, we comprehensively analyzed
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CRISPR-Cas9 screening identifies KRAS-induced COX-2 as a driver of immunotherapy resistance in lung cancer Cancer Res. (IF 11.2) Pub Date : 2024-04-18 Jesse Boumelha, Andrea de Castro, Nourdine Bah, Hongui Cha, Sophie de Carné Trécesson, Sareena Rana, Mona Tomaschko, Panayiotis Anastasiou, Edurne Mugarza, Christopher Moore, Robert Goldstone, Philip East, Kevin Litchfield, Se-Hoon Lee, Miriam Molina-Arcas, Julian Downward
Oncogenic KRAS impairs anti-tumor immune responses. As effective strategies to combine KRAS inhibitors and immunotherapies have so far proven elusive, a better understanding of how oncogenic KRAS drives immune evasion is needed to identify approaches that could sensitize KRAS-mutant lung cancer to immunotherapy. In vivo CRISPR-Cas9 screening in an immunogenic murine lung cancer model identified mechanisms
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CD106 in tumor-specific exhausted CD8+ T cells mediates immunosuppression by inhibiting TCR signaling Cancer Res. (IF 11.2) Pub Date : 2024-04-18 Yuto Naoi, Takao Morinaga, Joji Nagasaki, Ryo Ariyasu, Youki Ueda, Kazuo Yamashita, Wenhao Zhou, Shusuke Kawashima, Katsushige Kawase, Akiko Honobe-Tabuchi, Takehiro Ohnuma, Tatsuyoshi Kawamura, Yoshiyasu Umeda, Yu Kawahara, Yasuhiro Nakamura, Yukiko Kiniwa, Osamu Yamasaki, Satoshi Fukushima, Masahito Kawazu, Yutaka Suzuki, Hiroyoshi Nishikawa, Toyoyuki Hanazawa, Mizuo Ando, Takashi Inozume, Yosuke
T cell exhaustion is a major contributor to immunosuppression in the tumor microenvironment (TME). Blockade of key regulators of T cell exhaustion, such as PD-1, can reinvigorate tumor-specific T cells and activate anti-tumor immunity in various types of cancer. Here, we identified that CD106 was specifically expressed in exhausted CD8+ T cells in the TME using single-cell RNA-sequencing. High CD106
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PARP-ish: Gaps in Molecular Understanding and Clinical Trials Targeting PARP Exacerbate Racial Disparities in Prostate Cancer Cancer Res. (IF 11.2) Pub Date : 2024-04-18 Moriah Cunningham, Matthew J. Schiewer
PARP is a nuclear enzyme with a major function in the DNA damage response. PARP inhibitors (PARPi) have been developed for treating tumors harboring homologous recombination repair (HRR) defects that lead to a dependency on PARP. There are currently three PARPi approved for use in advanced prostate cancer (PCa), and several others are in clinical trials for this disease. Recent clinical trial results
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Deuterium metabolic imaging differentiates glioblastoma metabolic subtypes and detects early response to chemoradiotherapy Cancer Res. (IF 11.2) Pub Date : 2024-04-18 Jacob Chen Ming Low, Jianbo Cao, Friederike Hesse, Alan J. Wright, Anastasia Tsyben, Islam Alshamleh, Richard Mair, Kevin M. Brindle
Metabolic subtypes of glioblastoma have different prognoses and responses to treatment. Deuterium metabolic imaging with 2H-labeled substrates is a potential approach to stratify patients into metabolic subtypes for targeted treatment. Here, we used 2H magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) measurements of [6,6’-2H2]glucose metabolism to identify metabolic subtypes and
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The circMYBL2-encoded p185 protein suppresses colorectal cancer progression by inhibiting serine biosynthesis Cancer Res. (IF 11.2) Pub Date : 2024-04-18 Ning Zhao, Yinghao Cao, Ruikang Tao, Xiuxian Zhu, Runze Li, Yajun Chen, Kaixiong Tao, Lei Li, Hengyu Chen, Xianxiong Ma
Circular RNAs (circRNAs) are a class of covalently closed single-stranded loop RNAs that have been implicated to play a functional role in almost all types of cancers. Previous studies have revealed that circMYBL2 acts as a tumor-promoting circRNA. Here, we found that circMYBL2 in colorectal cancer (CRC) encodes a 185-amino acid protein, p185. Functionally, circMYBL2-encoded p185 suppressed the growth
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Fc-silent anti-TIGIT antibodies potentiate anti-tumor immunity without depleting regulatory T cells Cancer Res. (IF 11.2) Pub Date : 2024-04-18 Dana Piovesan, Amber E. de Groot, Soonweng Cho, Amy E. Anderson, Rebecca D. Ray, Amita Patnaik, Paul G. Foster, Casey G. Mitchell, Alejandra Y. Lopez Espinoza, Wandi S. Zhu, Carlo E. Stagnaro, Hema Singh, Xiaoning Zhao, Lisa Seitz, Nigel P. Walker, Matthew J. Walters, Kelsey E. Sivick
TIGIT is an inhibitory receptor on immune cells that outcompetes an activating receptor, CD226, for shared ligands. Tumor-infiltrating lymphocytes express TIGIT and CD226 on regulatory T cells (Treg) and on CD8+ T cells with tumor-reactive or exhausted phenotypes, supporting the potential of therapeutically targeting TIGIT to enhance anti-tumor immunity. To optimize the efficacy of therapeutic antibodies
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Omental preadipocytes stimulate matrix remodeling and IGF signaling to support ovarian cancer metastasis Cancer Res. (IF 11.2) Pub Date : 2024-04-18 Jennifer A. Waters, Mikella Robinson, Omar Lujano-Olazaba, Cassidy Lucht, Samuel F. Gilbert, Carrie D. House
Ovarian cancer can metastasize to the omentum, which is associated with a complex tumor microenvironment. Omental stromal cells facilitate ovarian cancer colonization by secreting cytokines and growth factors. Improved understanding of the tumor supportive functions of specific cell populations in the omentum could identify strategies to prevent and treat ovarian cancer metastasis. Here, we showed
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Pushing the Frontiers of Cancer Research: Highlights from the Frontiers in Cancer Science Conference 2023 Cancer Res. (IF 11.2) Pub Date : 2024-04-15 Yi Fei Lee, Leilei Chen, Valerie Chew, Edward Kai-Hua Chow, Lih-Wen Deng, Walter Hunziker, Ann Siew Gek Lee, Geraldine Leong, Joanne Ngeow, Shazib Pervaiz, Kanaga Sabapathy, Anders J. Skanderup, Raghav Sundar, Yvonne Tay, David M. Virshup, Sunny H. Wong, Vinay Tergaonkar, Wai Leong Tam
The 15th annual Frontiers in Cancer Science (FCS) conference gathered scientific experts who shared the latest research converging upon several themes of cancer biology. These themes included the dysregulation of metabolism, cell death, and other signaling processes in cancer cells; using patient “omics” datasets and single-cell and spatial approaches to investigate heterogeneity, understand therapy
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A Path to Persistence after EGFR Inhibition Cancer Res. (IF 11.2) Pub Date : 2024-04-15 Purva H. Rumde, Timothy F. Burns
Residual cancer cells persist even after targeted therapies, serving as a reservoir for the subsequent acquisition of genetic alterations that lead to acquired drug resistance and tumor relapse. These initial drug-tolerant persisters (DTP) are phenotypically heterogenous with transient phenotypes attributed to epigenetic, metabolic, and cell-cycle changes. DTPs are responsible for the inevitable relapse
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Unlocking the Role of Age-Related Changes to Fibroblasts in Pancreatic Cancer Cancer Res. (IF 11.2) Pub Date : 2024-04-15 Achinoam Isaacson, Debra Barki, Ruth Scherz-Shouval
Pancreatic cancer prevalence increases with age, and disease prognosis is poorer in older individuals. The increased prevalence is driven, undoubtedly, by the multistep accumulation of oncogenic mutations in cancer cells with age. However, fibroblasts are major constituents and key players in pancreatic cancer, and they too undergo age-related changes that may contribute to disease severity. In this
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Proteogenomic Characterization Reveals Estrogen Signaling as a Target for Never-Smoker Lung Adenocarcinoma Patients without EGFR or ALK Alterations Cancer Res. (IF 11.2) Pub Date : 2024-04-12 Seung-Jin Park, Shinyeong Ju, Sung-Ho Goh, Byoung-Ha Yoon, Jong-Lyul Park, Jeong-Hwan Kim, Seonjeong Lee, Sang-Jin Lee, Yumi Kwon, Wonyeop Lee, Kyung Chan Park, Geon Kook Lee, Seog Yun Park, Sunshin Kim, Seon-Young Kim, Ji-Youn Han, Cheolju Lee
Never-smoker lung adenocarcinoma (NSLA) is prevalent in Asian populations, particularly in women. EGFR mutations and anaplastic lymphoma kinase (ALK) fusions are major genetic alterations observed in NSLA, and NSLA with these alterations have been well studied and can be treated with targeted therapies. To provide insights into the molecular profile of NSLA without EGFR and ALK alterations (NENA),
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MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer Cancer Res. (IF 11.2) Pub Date : 2024-04-09 Si Min Zheng, Yu Chen Feng, Qin Zhu, Ruo Qi Li, Qian Qian Yan, Liu Teng, Yi Meng Yue, Man Man Han, Kaihong Ye, Sheng Nan Zhang, Teng Fei Qi, Cai Xia Tang, Xiao Hong Zhao, Yuan Yuan Zhang, Liang Xu, Ran Xu, Jun Xing, Mark Baker, Tao Liu, Rick F. Thorne, Lei Jin, Thomas Preiss, Xu Dong Zhang, Shundong Cang, Jin Nan Gao
Patients with triple-negative breast cancer (TNBC) have a poor prognosis due to the lack of effective molecular targets for therapeutic intervention. Here we found that the long noncoding RNA (lncRNA) MILIP supports TNBC cell survival, proliferation, and tumorigenicity by complexing with transfer RNAs (tRNA) to promote protein production, thus representing a potential therapeutic target in TNBC. MILIP
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Ketogenic diet alters the epigenetic and immune landscape of prostate cancer to overcome resistance to immune checkpoint blockade therapy Cancer Res. (IF 11.2) Pub Date : 2024-04-08 Sean Murphy, Sharif Rahmy, Dailin Gan, Guoqiang Liu, Yini Zhu, Maxim Manyak, Loan Duong, Jianping He, James H. Schofield, Zachary T. Schafer, Jun Li, Xuemin Lu, Xin Lu
Resistance to immune checkpoint blockade (ICB) therapy represents a formidable clinical challenge limiting the efficacy of immunotherapy. In particular, prostate cancer (PCa) poses a challenge for ICB therapy due to its immunosuppressive features. A ketogenic diet (KD) has been reported to enhance response to ICB therapy in some other cancer models. However, adverse effects associated with continuous
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How Artificial Intelligence Unravels the Complex Web of Cancer Drug Response Cancer Res. (IF 11.2) Pub Date : 2024-04-08 Olivier Elemento
The intersection of precision medicine and artificial intelligence (AI) holds profound implications for cancer treatment, with the potential to significantly advance our understanding of drug responses based on the intricate architecture of tumor cells. A recent study by Park and colleagues titled "A deep learning model of tumor cell architecture elucidates response and resistance to CDK4/6 inhibitors
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Integrin αvβ3 Upregulation in Response to Nutrient Stress Promotes Lung Cancer Cell Metabolic Plasticity Cancer Res. (IF 11.2) Pub Date : 2024-04-08 Arin Nam, Shashi Jain, Chengsheng Wu, Alejandro Campos, Ryan M. Shepard, Ziqi Yu, Joshua P. Reddy, Tami Von Schalscha, Sara M. Weis, Mark Onaitis, Hiromi I. Wettersten, David A. Cheresh
Cancer stem/tumor-initiating cells display stress tolerance and metabolic flexibility to survive in a harsh environment with limited nutrient and oxygen availability. The molecular mechanisms underlying this phenomenon could provide targets to prevent metabolic adaptation and halt cancer progression. Here, we showed in cultured cells and live human surgical biopsies of non–small cell lung cancer that
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Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial–Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma Cancer Res. (IF 11.2) Pub Date : 2024-04-08 Samantha Guinn, Benedict Kinny-Köster, Joseph A. Tandurella, Jacob T. Mitchell, Dimitrios N. Sidiropoulos, Melanie Loth, Melissa R. Lyman, Alexandra B. Pucsek, Daniel J. Zabransky, Jae W. Lee, Emma Kartalia, Mili Ramani, Toni T. Seppälä, Christopher Cherry, Reecha Suri, Haley Zlomke, Jignasha Patel, Jin He, Christopher L. Wolfgang, Jun Yu, Lei Zheng, David P. Ryan, David T. Ting, Alec Kimmelman, Anuj
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas
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Oncogene-driven non-small cell lung cancers in patients with a history of smoking lack smoking-induced mutations Cancer Res. (IF 11.2) Pub Date : 2024-04-08 Chen-Yang Huang, Nanhai Jiang, Meixin Shen, Gillianne G. Lai, Aaron C. Tan, Amit Jain, Stephanie P. Saw, Mei Kim Ang, Quan Sing Ng, Darren W. Lim, Ravindran Kanesvaran, Eng Huat Tan, Wan Ling Tan, Boon-Hean Ong, Kevin L. Chua, Devanand Anantham, Angela M. Takano, Kiat Hon Lim, Wai Leong Tam, Ngak Leng Sim, Anders J. Skanderup, Daniel S. Tan, Steven G. Rozen
Non-small cell lung cancers (NSCLCs) in non-smokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in non-smokers, alterations in these “non-smoking-related oncogenes” (NSROs) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared to typical-smoking
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Comprehensive Transcriptomic Analysis of EWSR1::WT1 Targets Identifies CDK4/6 Inhibitors as an Effective Therapy for Desmoplastic Small Round Cell Tumors Cancer Res. (IF 11.2) Pub Date : 2024-04-08 Justin W. Magrath, Shruthi Sanjitha Sampath, Dane A. Flinchum, Alifiani B. Hartono, Ilon N. Goldberg, Julia R. Boehling, Suzana D. Savkovic, Sean B. Lee
Desmoplastic small round cell tumors (DSRCT) are a type of aggressive, pediatric sarcoma characterized by the EWSR1::WT1 fusion oncogene. Targeted therapies for DSRCT have not been developed, and standard multimodal therapy is insufficient, leading to a 5-year survival rate of only 15% to 25%. Here, we depleted EWSR1::WT1 in DSRCT and established its essentiality in vivo. Transcriptomic analysis revealed
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Integration of pan-cancer cell line and single-cell transcriptomic profiles enables inference of therapeutic vulnerabilities in heterogeneous tumors Cancer Res. (IF 11.2) Pub Date : 2024-04-06 Weijie Zhang, Danielle Maeser, Adam Lee, Yingbo Huang, Robert F. Gruener, Israa G. Abdelbar, Sampreeti Jena, Anand G. Patel, R. Stephanie Huang
Single-cell RNA-sequencing (scRNA-seq) greatly advanced the understanding of intratumoral heterogeneity by identifying distinct cancer cell subpopulations. However, translating biological differences into treatment strategies is challenging due to a lack of tools to facilitate efficient drug discovery that tackles heterogeneous tumors. Developing such approaches requires accurate prediction of drug
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Mathematical Model-Driven Deep Learning Enables Personalized Adaptive Therapy Cancer Res. (IF 11.2) Pub Date : 2024-04-03 Kit Gallagher, Maximilian A. Strobl, Derek S. Park, Fabian C. Spoendlin, Robert A. Gatenby, Philip K. Maini, Alexander R. Anderson
Standard-of-care treatment regimens have long been designed for maximal cell killing, yet these strategies often fail when applied to metastatic cancers due to the emergence of drug resistance. Adaptive treatment strategies have been developed as an alternative approach, dynamically adjusting treatment to suppress the growth of treatment-resistant populations and thereby delay, or even prevent, tumor
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Personalized Cancer Vaccines Directed against Tumor Mutations: Building Evidence from Mice to Humans Cancer Res. (IF 11.2) Pub Date : 2024-04-01 Edward F. Fritsch, Patrick A. Ott
Personalized vaccines directed to tumor mutations have recently gained significant momentum. On the basis of the concept of stimulating T-cell responses against neoantigens encoded by a tumor's host of personal mutations, these vaccines utilize genome or exome sequencing, mutation calling, and epitope prediction followed by manufacturing of a customized vaccine for each patient. In their 2012 Cancer
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Cancer Builds a Noxious Partnership with Psychologic Stress Cancer Res. (IF 11.2) Pub Date : 2024-04-01 Claire Magnon
I was recently surprised to hear a medical doctor on a TV show refute the role of stress in cancer, assuming that “the whole population would have cancer if this was the case.” This statement illustrates a long and winding road since Hippocrates suggested the potential relationship between cancer and psychologic disturbances. The 20th and 21st centuries have finally witnessed the evidence of how physical
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The Rigidity Connection: Matrix Stiffness and Its Impact on Cancer Progression Cancer Res. (IF 11.2) Pub Date : 2024-04-01 Anna Yui, Madeleine J. Oudin
The extracellular matrix (ECM) has always been studied in the context of the structural support it provides tissues. However, more recently, it has become clear that ECM proteins do more to regulate biological processes relevant to cancer progression: from activating complex signaling pathways to presenting soluble growth factors. In 2009, Ulrich and colleagues provided evidence that the physical properties
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Exploring Ferroptosis-Inducing Therapies for Cancer Treatment: Challenges and Opportunities Cancer Res. (IF 11.2) Pub Date : 2024-04-01 Guang Lei, Boyi Gan
Conventional cancer therapies typically aim to eliminate tumor cells by inducing cell death. The emergence of resistance to these standard treatments has spurred a shift in focus toward exploring alternative cell death pathways beyond apoptosis. Ferroptosis—an iron-dependent regulated cell death triggered by lipid peroxide accumulation—has gained prominence in cancer research in recent years. Ferroptosis-inducing
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Targeting Metabolic Dependencies Fueling the TCA Cycle to Circumvent Therapy Resistance in Acute Myeloid Leukemia Cancer Res. (IF 11.2) Pub Date : 2024-04-01 Emeline Boët, Jean-Emmanuel Sarry
Acute myeloid leukemia (AML) is one of the most prevalent blood cancers, characterized by a dismal survival rate. This poor outcome is largely attributed to AML cells that persist despite treatment and eventually result in relapse. Relapse-initiating cells exhibit diverse resistance mechanisms, encompassing genetic factors and, more recently discovered, nongenetic factors such as metabolic adaptations
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The deep learning framework iCanTCR enables early cancer detection using the T cell receptor repertoire in peripheral blood Cancer Res. (IF 11.2) Pub Date : 2024-03-27 Yideng Cai, Meng Luo, Wenyi Yang, Chang Xu, Pingping Wang, Guangfu Xue, Xiyun Jin, Rui Cheng, Jinhao Que, Wenyang Zhou, Boran Pang, Shouping Xu, Yu Li, Qinghua Jiang, Zhaochun Xu
T cells recognize tumor antigens and initiate an anti-cancer immune response in the very early stages of tumor development, and the antigen specificity of T cells is determined by the T cell receptor (TCR). Therefore, monitoring changes in the TCR repertoire in peripheral blood may offer a strategy to detect various cancers at a relatively early stages. Here, we developed the deep learning framework
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Regular use of aspirin and statins reduces the risk of cancer in individuals with systemic inflammatory diseases Cancer Res. (IF 11.2) Pub Date : 2024-03-27 Jia-Run Lin, Duan-Duan Han, Wei Wei, Qin Zeng, Zi-Xuan Rong, Xue Bai, Yan-Pei Zhang, Jian Wang, Xiao-Ting Cai, Xu-Guang Rao, Si-Cong Ma, Zhong-Yi Dong
Aspirin has shown potential for cancer prevention, but a recent large randomized controlled trial found no evidence for a reduction in cancer risk. Given the anti-inflammatory effects of aspirin, systemic inflammatory diseases (SIDs), such as osteoporosis, cardiovascular diseases, and metabolic diseases, could potentially modify the aspirin-cancer link. To investigate the impact of aspirin in people
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Cancer cells hijack physiological metabolic signals to seed liver metastasis Cancer Res. (IF 11.2) Pub Date : 2024-03-27 Andres Rettig, Karuna Ganesh
Metastasis arises from cancer-cell intrinsic adaptations and permissive tumor microenvironments (TME) that are distinct across different organs. Deciphering the mechanisms underpinning organotropism could provide novel preventive and therapeutic strategies for cancer patients. Rogava and colleagues identified Pip4kc as a driver of liver metastasis, acting by sensitizing cancer cells to insulin-dependent
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NPEPPS Is a Druggable Driver of Platinum Resistance Cancer Res. (IF 11.2) Pub Date : 2024-03-27 Robert T. Jones, Mathijs Scholtes, Andrew Goodspeed, Maryam Akbarzadeh, Saswat Mohapatra, Lily Elizabeth Feldman, Hedvig Vekony, Annie Jean, Charlene B. Tilton, Michael V. Orman, Shahla Romal, Cailin Deiter, Tsung Wai Kan, Nathaniel Xander, Stephanie P. Araki, Molishree Joshi, Mahmood Javaid, Eric T. Clambey, Ryan Layer, Teemu D. Laajala, Sarah J. Parker, Tokameh Mahmoudi, Tahlita C.M. Zuiverloon,
There is an unmet need to improve the efficacy of platinum-based cancer chemotherapy, which is used in primary and metastatic settings in many cancer types. In bladder cancer, platinum-based chemotherapy leads to better outcomes in a subset of patients when used in the neoadjuvant setting or in combination with immunotherapy for advanced disease. Despite such promising results, extending the benefits
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m6A modification promotes EMT and metastasis of castration-resistant prostate cancer by upregulating NFIB Cancer Res. (IF 11.2) Pub Date : 2024-03-27 Feng Shu, Hao Liu, Xiaohui Chen, Ye Liu, Jiangli Zhou, Lei Tang, Wanwei Cao, Shanshan Yang, Yili Long, Rongna Li, Hao Wang, Hongsheng Wang, Guanmin Jiang
The widespread use of androgen receptor (AR) signaling inhibitors has led to an increased incidence of AR-negative castration-resistant prostate cancer (CRPC), limiting effective treatment and patient survival. A more comprehensive understanding of the molecular mechanisms supporting AR-negative CRPC could reveal therapeutic vulnerabilities to improve treatment. This study showed that the transcription
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A subpopulation of luminal progenitors secretes pleiotrophin to promote angiogenesis and metastasis in inflammatory breast cancer Cancer Res. (IF 11.2) Pub Date : 2024-03-20 Mengmeng Zhang, Kaiwen Zhou, Zilin Wang, Ting Liu, Laura E. Stevens, Filipa Lynce, Wendy Y. Chen, Sui Peng, Yubin Xie, Duanyang Zhai, Qianjun Chen, Yawei Shi, Huijuan Shi, Zhongyu Yuan, Xiaoping Li, Juan Xu, Zhenhai Cai, Jianping Guo, Nan Shao, Ying Lin
Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer characterized by rapidly arising diffuse erythema and edema. Genomic studies have not identified consistent alterations and mechanisms that differentiate IBC from non-IBC tumors, suggesting that the microenvironment could be a potential driver of IBC phenotypes. Here, using single-cell RNA sequencing, multiplex staining
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Cigarette smoking and e-cigarette use induce shared DNA methylation changes linked to carcinogenesis Cancer Res. (IF 11.2) Pub Date : 2024-03-19 Chiara Herzog, Allison Jones, Iona Evans, Janhavi R. Raut, Michal Zikan, David Cibula, Andrew Wong, Hermann Brenner, Rebecca C. Richmond, Martin Widschwendter
Tobacco use is a major modifiable risk factor for adverse health outcomes, including cancer, and elicits profound epigenetic changes thought to be associated with long-term cancer risk. While electronic cigarettes (e-cigarettes) have been advocated as harm reduction alternatives to tobacco products, recent studies have revealed potential detrimental effects, highlighting the urgent need for further