-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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),
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
Oncogenic KRAS induces arginine auxotrophy and confers a therapeutic vulnerability to SLC7A1 inhibition in non-small cell lung cancer Cancer Res. (IF 11.2) Pub Date : 2024-03-19 Xiameng Gai, Yingluo Liu, Xiaojing Lan, Luoyi Chen, Tao Yuan, Jun Xu, Yize Li, Ying Zheng, Yiyang Yan, Liya Yang, Yixian Fu, Shuai Tang, Siyuwei Cao, Xiaoyang Dai, Hong Zhu, Meiyu Geng, Jian Ding, Congying Pu, Min Huang
The urea cycle is frequently rewired in cancer cells to meet the metabolic demands of cancer. Elucidation of the underlying mechanism by which oncogenic signaling mediates urea cycle reprogramming could help identify targetable metabolic vulnerabilities. In this study, we discovered that oncogenic activation of KRAS in non-small cell lung cancer (NSCLC) silenced the expression of argininosuccinate
-
Oncogenic cell tagging and single-cell transcriptomics reveal cell type-specific and time-resolved responses to Vhl inactivation in the kidney Cancer Res. (IF 11.2) Pub Date : 2024-03-19 Samvid Kurlekar, Joanna D. C. C. Lima, Ran Li, Olivia Lombardi, Norma Masson, Ayslan B. Barros, Virginia Pontecorvi, David R. Mole, Christopher W. Pugh, Julie Adam, Peter J. Ratcliffe
Defining the initial events in oncogenesis and the cellular responses they entrain, even in advance of morphological abnormality, is a fundamental challenge in understanding cancer initiation. As a paradigm to address this, we longitudinally studied the changes induced by loss of the tumor suppressor gene von Hippel Lindau (VHL), which ultimately drives clear cell renal cell carcinoma. Vhl inactivation
-
ATG-101 is a tetravalent PD-L1×4-1BB bispecific antibody that stimulates anti-tumor immunity through PD-L1 blockade and PD-L1-directed 4-1BB activation Cancer Res. (IF 11.2) Pub Date : 2024-03-19 Hui Yuwen, Huajing Wang, Tengteng Li, Yijing Ren, Yun-Kai Zhang, Peng Chen, Ao Sun, Gang Bian, Bohua Li, David Flowers, Marc Presler, Kalyanasundaram Subramanian, Jia Xue, Jingjing Wang, Kevin Lynch, Jay Mei, Xiaowen He, Bo Shan, Bing Hou
Immune checkpoint inhibitors (ICI) have transformed cancer treatment. However, only a minority of patients achieve a profound response. Many patients are innately resistant while others acquire resistance to ICIs. Furthermore, hepatotoxicity and suboptimal efficacy have hampered the clinical development of agonists of 4-1BB, a promising immune stimulating target. To effectively target 4-1BB and treat
-
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
-
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, Erin 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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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)
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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