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Coagulation factor X promotes resistance to androgen-deprivation therapy in prostate cancer Cancer Cell (IF 48.8) Pub Date : 2024-09-19 Bianca Calì, Martina Troiani, Silvia Bressan, Giuseppe Attanasio, Sara Merler, Viola Moscarda, Simone Mosole, Elena Ricci, Christina Guo, Wei Yuan, Lewis Gallagher, Arian Lundberg, Ilona Bernett, Ines Figueiredo, Rydell Alvarez Arzola, Ernesto Bermudez Abreut, Mariantonietta D’Ambrosio, Nicolò Bancaro, Daniela Brina, Sara Zumerle, Andrea Alimonti
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Fusobacterium nucleatum facilitates anti-PD-1 therapy in microsatellite stable colorectal cancer Cancer Cell (IF 48.8) Pub Date : 2024-09-19 Xueliang Wang, Yi Fang, Wei Liang, Chi Chun Wong, Huanlong Qin, Yaohui Gao, Meinong Liang, Lei Song, Yongxin Zhang, Miao Fan, Chuanfa Liu, Harry Cheuk-Hay Lau, Lixia Xu, Xiaoxing Li, Wu Song, Junlin Wang, Na Wang, Tao Yang, Mengmiao Mo, Xiang Zhang, Jun Yu
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Cross-tissue human fibroblast atlas reveals myofibroblast subtypes with distinct roles in immune modulation Cancer Cell (IF 48.8) Pub Date : 2024-09-19 Yang Gao, Jianan Li, Wenfeng Cheng, Tian Diao, Huilan Liu, Yufei Bo, Chang Liu, Wei Zhou, Minmin Chen, Yuanyuan Zhang, Zhihua Liu, Weidong Han, Rufu Chen, Jirun Peng, Linnan Zhu, Wenhong Hou, Zemin Zhang
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A new standard of care for leiomyosarcoma Nat. Rev. Clin. Oncol. (IF 81.1) Pub Date : 2024-09-19 Peter Sidaway
Patients with advanced-stage leiomyosarcoma, a type of soft-tissue sarcoma that occurs predominantly in uterine locations, typically receive doxorubicin and have a median overall survival (OS) of ~20 months. Now, data from a randomized phase III trial demonstrate that adding trabectedin to doxorubicin significantly improves OS. A total of 150 patients with previously untreated locally advanced or metastatic
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VIBRANT: mapping cell phenotypes using vibrational spectroscopy Nat. Rev. Cancer (IF 72.5) Pub Date : 2024-09-19 Xinwen Liu
In this Tools of the Trade article, Xinwen Liu describes the development of VIBRANT, a vibrational spectroscopy method for high-content phenotypic profiling, and highlights its use to predict drug mechanisms of action or identify potential drug candidates.
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The recruitment of metastasis-associated monocytes Nat. Rev. Cancer (IF 72.5) Pub Date : 2024-09-18 Suhn Hyung Kim, Keehoon Jung
In this Journal Club, Kim and Jung discuss a study that demonstrates the role of CCL2 in recruiting monocytes to the metastasic site.
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Reviewer acknowledgement 2024 CA: Cancer J. Clin. (IF 503.1) Pub Date : 2024-09-18
In order to maintain the high standards of CA’s content, the Editors of CA rely on the knowledge and dedication of many experts in deciding which topics to pursue, which manuscripts to publish, and what modifications to make to ensure medical and scientific accuracy and suitability for our readers. We thank our Associate Editors and our Editorial Advisory Board, who continue to provide these services
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Altered metabolism in cancer: insights into energy pathways and therapeutic targets Mol. Cancer (IF 27.7) Pub Date : 2024-09-18 Muhammad Tufail, Can-Hua Jiang, Ning Li
Cancer cells undergo significant metabolic reprogramming to support their rapid growth and survival. This study examines important metabolic pathways like glycolysis, oxidative phosphorylation, glutaminolysis, and lipid metabolism, focusing on how they are regulated and their contributions to the development of tumors. The interplay between oncogenes, tumor suppressors, epigenetic modifications, and
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Spatiotemporal metabolomic approaches to the cancer-immunity panorama: a methodological perspective Mol. Cancer (IF 27.7) Pub Date : 2024-09-18 Yang Xiao, Yongsheng Li, Huakan Zhao
Metabolic reprogramming drives the development of an immunosuppressive tumor microenvironment (TME) through various pathways, contributing to cancer progression and reducing the effectiveness of anticancer immunotherapy. However, our understanding of the metabolic landscape within the tumor-immune context has been limited by conventional metabolic measurements, which have not provided comprehensive
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A Paradigm Shift in Tumor Immunology: Th17 Cells and TGF-β in Intestinal Cancer Initiation Cancer Res. (IF 12.5) Pub Date : 2024-09-18 Megan M. Wyatt, Chrystal M. Paulos
Cancer remains one of the most complex challenges in modern medicine, with intricate relationships between immune responses and tumor development. This article examines a groundbreaking study by Fesneau, Thevin and colleagues, published in Nature Immunology. This elegant body of work explores the link between chronic inflammation and cancer, particularly focusing on Th17 cells involved in intestinal
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Inhibition of JNK Signaling Overcomes Cancer-Associated Fibroblast-Mediated Immunosuppression and Enhances the Efficacy of Immunotherapy in Bladder Cancer Cancer Res. (IF 12.5) Pub Date : 2024-09-18 Chengying Cui, Haojie Zhang, Congcong Yang, Mingwei Yin, Xinkun Teng, Miaomiao Yang, Dejie Kong, Jinzhi Zhang, Weidong Peng, Zhimin Chu, Jingjing Wang, Yating Sun, Liping Kang, Bin Lyu, Qian Gao, Mingqing Wu, Yongqiang Wang, Yang Li
Currently, only 20-40% of cancer patients benefit from immune checkpoint inhibitors. Understanding the mechanisms underlying the immunosuppressive tumor microenvironment (TME) and characterizing dynamic changes in the immunological landscape during treatment are critical for improving responsiveness to immunotherapy. Here, we identified JNK signaling in cancer-associated fibroblasts (CAFs) as a regulator
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AACR Cancer Progress Report 2024: Inspiring Science-Fueling Progress-Revolutionizing Care. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-18 Patrick A Williams,Sayyed Kaleem Zaidi,Rajarshi Sengupta
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Strength of Evidence Underlying the CMS-FDA Parallel Review of Comprehensive Genomic Profiling Tests in the Cancer Setting J. Natl. Cancer Inst. (IF 9.9) Pub Date : 2024-09-18 Sydnie Stackland, Dominic Schnabel, Michaela Dinan, Carolyn J Presley, Cary P Gross
Background Although use of comprehensive genomic profiling (CGP) was approved by a novel CMS/FDA parallel review process, the quality of the supporting evidence is unclear. We evaluated the rigor of the peer-reviewed literature cited in the National Coverage Determination Memorandum for the FoundationOne CDx (F1CDx). Methods We identified studies cited in the memorandum. Two independent researchers
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mLumiOpto is a Mitochondrial-Targeted Gene Therapy for Treating Cancer Cancer Res. (IF 12.5) Pub Date : 2024-09-17 Kai Chen, Patrick Ernst, Anusua Sarkar, Seulhee Kim, Yingnan Si, Tanvi Varadkar, Matthew D. Ringel, Xiaoguang Liu, Lufang Zhou
Mitochondria are important in various aspects of cancer development and progression. Targeting mitochondria in cancer cells holds great therapeutic promise, yet current strategies to specifically and effectively destroy cancer mitochondria in vivo are limited. Here, we developed mLumiOpto, an innovative mitochondrial-targeted luminoptogenetics gene therapy designed to directly disrupt the inner mitochondrial
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CircRREB1 Mediates Metabolic Reprogramming and Stemness Maintenance to Facilitate Pancreatic Ductal Adenocarcinoma Progression Cancer Res. (IF 12.5) Pub Date : 2024-09-17 Zeyin Rong, Jin Xu, Jianhui Yang, Wei Wang, Rong Tang, Zifeng Zhang, Zhen Tan, Qingcai Meng, Jie Hua, Jiang Liu, Bo Zhang, Chen Liang, Xianjun Yu, Si Shi
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumor with limited treatment options and poor patient survival. Circular RNAs (circRNAs) play crucial regulatory roles in the occurrence and development of various cancers, including PDAC. Here, using circRNA sequencing of diverse PDAC samples, we identified circRREB1 as an oncogenic circRNA that is significantly upregulated in PDAC and is
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Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer Cancer Res. (IF 12.5) Pub Date : 2024-09-17 Koki Oyama, Kohei Nakata, Chikanori Tsutsumi, Masataka Hayashi, Bo Zhang, Yuki Mochida, Tomohiko Shinkawa, Kento Hirotaka, Pingshan Zhong, Satomi Date, Haizhen Luo, Akihiro Kubo, Nobuhiro Higashijima, Yutaka Yamada, Toshiya Abe, Noboru Ideno, Kazuhiro Koikawa, Chika Iwamoto, Naoki Ikenaga, Kenoki Ohuchida, Hideya Onishi, Takashi Morisaki, Keiji Kuba, Yoshinao Oda, Masafumi Nakamura
The effect of immune checkpoint inhibitors is extremely limited in patients with pancreatic ductal adenocarcinoma (PDAC) due to the suppressive tumor immune microenvironment (TIME). Autophagy, which has been shown to play a role in anti-tumor immunity, has been proposed as a therapeutic target for PDAC. Here, single-cell RNA-sequencing of autophagy-deficient murine PDAC tumors revealed that autophagy
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Precise In Situ Delivery of a Photo-enhanceable Inflammasome-Activating Nanovaccine Activates Anti-cancer Immunity Cancer Res. (IF 12.5) Pub Date : 2024-09-17 Yang Zhou, Li Pang, Tao Ding, Kang Chen, Jinzhao Liu, Meicen Wu, Weiping Wang, Kwan Man
A variety of state-of-the-art nanovaccines (NVs) combined with immunotherapies have recently been developed to treat malignant tumors, showing promising results. However, immunosuppression in the tumor microenvironment (TME) restrains cytotoxic T cells infiltration and limits the efficacy of immunotherapies in solid tumors. Therefore, tactics for enhancing antigen cross-presentation and reshaping the
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CD24-Targeted NIR-II Fluorescence Imaging Enables Early Detection of Colorectal Neoplasia Cancer Res. (IF 12.5) Pub Date : 2024-09-17 Xiaoyong Guo, Shuangling Luo, Xiaofeng Wang, Yingying Cui, Miaomiao Li, Zeyu Zhang, Lidan Fu, Caiguang Cao, Xiaojing Shi, Haifeng Liu, Yawei Qu, Xiangyu Gao, Zhenhua Hu, Jie Tian
Colorectal cancer (CRC) continues to be a major health issue even though screening methods have facilitated early detection. Despite the high sensitivity of white-light colonoscopy, it frequently overlooks invasive flat or depressed lesions, which can lead to the development of larger, advanced tumors. Fluorescence molecular imaging (FMI) offers a promising approach for early tumor detection by targeting
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Cancer in multi-lineage mosaic RASopathies due to pathogenic variants in HRAS or KRAS: a systematic review and meta-analysis Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-17 Jonas Windrich, Gina M. Ney, Philip S. Rosenberg, Jung Kim, Martin Zenker, Douglas R. Stewart, Christian P. Kratz
Purpose: To determine the cancer risk and spectrum in patients with multi-lineage mosaic RASopathies with pathogenic variants (PV) in HRAS or KRAS. Methods: We conducted a systematic literature review to identify multi-lineage mosaic RASopathy cases with a PV in HRAS or KRAS to create a retrospective cohort. We calculated cumulative incidence, cancer-free survival and hazard rates (HR) for cancer and
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A Phase I First-in-Human Study of ABBV-011, a Seizure-Related Homolog Protein 6-Targeting Antibody-Drug Conjugate, in Patients With Small Cell Lung Cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-17 Daniel Morgensztern, Neal Ready, Melissa L. Johnson, Afshin Dowlati, Noura Choudhury, David P. Carbone, Eric Schaefer, Susanne M. Arnold, Sonam Puri, Zofia Piotrowska, Aparna Hegde, Anne C. Chiang, Wade Iams, Anthony Tolcher, Kaname Nosaki, Toshiyuki Kozuki, Tianhong Li, Rafael Santana-Davila, Hiroaki Akamatsu, Haruyasu Murakami, Hiroshi Yokouchi, Song Wang, Jiuhong Zha, Rui Li, Randy R. Robinson,
Purpose: Seizure-related homolog protein 6 (SEZ6) is a novel target expressed in small cell lung cancer (SCLC). ABBV-011, a SEZ6-targeted antibody conjugated to calicheamicin, was evaluated in a phase I study (NCT03639194) in patients with relapsed/refractory SCLC. We report initial outcomes of ABBV-011 monotherapy. Patients and Methods: ABBV-011 was administered intravenously once every 3 weeks (Q3W)
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Clonal Hematopoiesis and Clinical Outcomes in Metastatic Castration-Resistant Prostate Cancer Patients Given Androgen Receptor Pathway Inhibitors (Alliance A031201) Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-17 Jeffrey L. Jensen, Olivia Bobek, Irenaeus C. C. Chan, Brian C. Miller, David W. Hillman, Glenn Heller, Todd Druley, Andrew J. Armstrong, Michael J. Morris, Matthew I. Milowsky, Himisha Beltran, Kelly L. Bolton, Catherine C. Coombs
Purpose: Mutations in hematopoietic progenitor cells accumulate with age leading to clonal expansion, termed clonal hematopoiesis (CH). CH in the general population is associated with hematopoietic neoplasms and reduced overall survival (OS), predominantly through cardiovascular adverse events (CVAE). Because androgen receptor pathway inhibitors (ARPI) used in metastatic castration-resistant prostate
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Multiomics Profiling Distinguishes Sebaceous Carcinoma from Benign Sebaceous Neoplasms and Provides Insight into the Genetic Evolution of Sebaceous Carcinogenesis Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-17 Gabriel J. Starrett, Brittany C. Baikie, Benjamin K. Stoff, Hans E. Grossniklaus, Inga Van Buren, Elizabeth G. Berry, Roberto A. Novoa, Kerri E. Rieger, Kavita Y. Sarin, Charles F. Lynch, Michael C. Royer, Mary L. Piaskowski, Isaac Brownell, Emily Y. Chu, Rama Godse, Suephy C. Chen, Kelly J. Yu, Alisa M. Goldstein, Eric A. Engels, Michael R. Sargen
Purpose: Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms
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Update on Whole-body MRI Surveillance for Pediatric Cancer Predisposition Syndromes Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-17 Mary-Louise C. Greer, Lisa J. States, David Malkin, Stephan D. Voss, Andrea S. Doria
Whole-body MRI (WBMRI) is an integral part of screening infants, children and adolescents for pre-symptomatic neoplasms in certain cancer predisposition syndromes (CPS). This includes Li-Fraumeni and Constitutional Mismatch Repair Deficiency syndromes, among others. The list of syndromes where WBMRI adds value, as part of a comprehensive surveillance protocol, continues to evolve in response to new
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Benefits and Harms of Hepatocellular Carcinoma Screening Outreach in Patients with Cirrhosis: A Multi-Center Randomized Clinical Trial J. Natl. Cancer Inst. (IF 9.9) Pub Date : 2024-09-17 Amit G Singal, Darine Daher, Manasa Narasimman, Sruthi Yekkaluri MHI, Yan Liu, Vanessa Cerda, Chaitra Banala, Aisha Khan, MinJae Lee, Karim Seif El Dahan, Caitlin C Murphy, Jennifer R Kramer, Ruben Hernaez
Background The value of hepatocellular carcinoma (HCC) screening is defined by the balance of benefits from early tumor detection vs harms due to false positive results. We evaluated the value of a mailed outreach strategy for HCC screening in patients with cirrhosis. Methods We conducted a multi-center pragmatic randomized clinical trial comparing mailed outreach for HCC screening (n = 1436) and usual
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County-level jail and state-level prison incarceration and cancer mortality in the United States J. Natl. Cancer Inst. (IF 9.9) Pub Date : 2024-09-17 Jingxuan Zhao, Sandhya Kajeepeta, Christopher R Manz, Xuesong Han, Leticia M Nogueira, Zhiyuan Zheng, Qinjin Fan, Kewei Sylvia Shi, Fumiko Chino, K Robin Yabroff
This study examined the association of county-level jail and state-level prison incarceration rates and cancer mortality rates in the United States. Incarceration rates (1995-2018) were sourced from national data and categorized into quartiles. County- and state-level mortality rates (2000-2019) with invasive cancer as the underlying cause of death were obtained from the National Vital Statistics System
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Unraveling the extracellular vesicle network: insights into ovarian cancer metastasis and chemoresistance Mol. Cancer (IF 27.7) Pub Date : 2024-09-16 Wei Dai, Jianwei Zhou, Ting Chen
Ovarian cancer (OC) is one of the most prevalent and lethal gynecological malignancies, with high mortality primarily due to its aggressive nature, frequent metastasis, and resistance to standard therapies. Recent research has highlighted the critical role of extracellular vesicles (EVs) in these processes. EVs, secreted by living organisms and carrying versatile and bioactive cargoes, play a vital
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The Pivotal Role of Germline BRCA2 Pathogenic Variants in “Apparently Sporadic” Pancreatic Cancer Cancer Res. (IF 12.5) Pub Date : 2024-09-16 Jonathan R. Brody, Alison P. Klein
In 1996, Goggins and colleagues demonstrated the importance of germline BRCA2 pathogenic variants in the development of apparently sporadic pancreatic ductal adenocarcinoma (PDAC). Previously, the group identified homozygous deletion of the 13q region in PDACs, enabling the identification of the BRCA2 gene. This 1996 article first revealed loss of BRCA2, both germline and somatic, as a key driver of
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Neutrophils in the premetastatic niche: key functions and therapeutic directions Mol. Cancer (IF 27.7) Pub Date : 2024-09-14 Jiachi Jia, Yuhang Wang, Mengjia Li, Fuqi Wang, Yingnan Peng, Junhong Hu, Zhen Li, Zhilei Bian, Shuaixi Yang
Metastasis has been one of the primary reasons for the high mortality rates associated with tumours in recent years, rendering the treatment of current malignancies challenging and representing a significant cause of recurrence in patients who have undergone surgical tumour resection. Halting tumour metastasis has become an essential goal for achieving favourable prognoses following cancer treatment
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Correction: Programmed death receptor (PD-)1/PD-ligand (L)1 in urological cancers: the “all-around warrior” in immunotherapy Mol. Cancer (IF 27.7) Pub Date : 2024-09-14 Qiang Liu, Yujing Guan, Shenglong Li
Correction: Mol Cancer 23, 183 (2024) https://doi.org/10.1186/s12943-024-02095-8 Following publication of the original article [1], the author reported that the published PDF version is incorrect as the information such as “(See Fig. 5)”, “(Fig. 4; Table 3)”, and “[170]” need to be removed and updated accordingly as shown below. The original article has been corrected. The sentences currently read:
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Allostatic Load, Genetic Susceptibility, Incidence Risk, and All-cause Mortality of Colorectal Cancer J. Natl. Cancer Inst. (IF 9.9) Pub Date : 2024-09-14 Jianhui Zhao, Erxu Xue, Siyun Zhou, Meng Zhang, Jing Sun, Yuqian Tan, Xue Li
Background Allostatic load (AL) reflects the cumulative burden of chronic stress throughout life, potentially influencing the onset and prognosis of cancer. However, the associations between AL, colorectal cancer (CRC) risk and all-cause mortality in patients with CRC remain unclear. Methods We analyzed the association between AL and CRC risk in 304,959 adults and all-cause mortality in 1,794 patients
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Histopathological response to chemotherapy and survival of mucinous type gastric cancer J. Natl. Cancer Inst. (IF 9.9) Pub Date : 2024-09-14 Irene A Caspers, Astrid E Slagter, Pauline A J Vissers, Martha Lopez-Yurda, Laurens V Beerepoot, Jelle P Ruurda, Grard A P Nieuwenhuijzen, Suzanne S Gisbertz, Mark I Van Berge Henegouwen, Henk H Hartgrink, Danny Goudkade, Liudmila L Kodach, Johanna W Van Sandick, Marcel Verheij, Rob H A Verhoeven, Annemieke Cats, Nicole C T Van Grieken
Background Data on the clinicopathological characteristics of mucinous gastric cancer (muc-GC) are limited. This study compares the clinical outcome and response to chemotherapy between patients with resectable muc-GC, intestinal (int-GC) and diffuse (dif-GC) gastric cancer. Methods Patients from the D1/D2 study or the CRITICS trial were included in exploratory surgery-alone (SAtest) or chemotherapy
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Dual HER2 inhibition: mechanisms of synergy, patient selection, and resistance Nat. Rev. Clin. Oncol. (IF 81.1) Pub Date : 2024-09-13 Adrienne G. Waks, Olga Martínez-Sáez, Paolo Tarantino, Fara Braso-Maristany, Tomás Pascual, Javier Cortés, Sara M. Tolaney, Aleix Prat
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Exosomal miR-4745-5p/3911 from N2-polarized tumor-associated neutrophils promotes gastric cancer metastasis by regulating SLIT2 Mol. Cancer (IF 27.7) Pub Date : 2024-09-13 Jiahui Zhang, Dan Yu, Cheng Ji, Maoye Wang, Min Fu, Yu Qian, Xiaoxin Zhang, Runbi Ji, Chong Li, Jianmei Gu, Xu Zhang
Tumor cells remodel the phenotype and function of tumor microenvironment (TME) cells to favor tumor progression. Previous studies have shown that neutrophils in TME are polarized to N2 tumor-associated neutrophils (TANs) by tumor derived factors, thus promoting tumor growth and metastasis, angiogenesis, therapy resistance, and immunosuppression. Exosomes act as critical intercellular messengers in
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Identification of microenvironment features associated with primary resistance to anti-PD-1/PD-L1 + antiangiogenesis in gastric cancer through spatial transcriptomics and plasma proteomics Mol. Cancer (IF 27.7) Pub Date : 2024-09-13 Sophie Cousin, Jean-Philippe Guégan, Kohei Shitara, Lola Jade Palmieri, Jean Philippe Metges, Simon Pernot, Shota Fukuoka, Shohei Koyama, Hiroyoshi Nishikawa, Carine A. Bellera, Antoine Adenis, Carlos A. Gomez-Roca, Philippe Alexandre Cassier, Antoine Hollebecque, Coralie Cantarel, Michèle Kind, Isabelle Soubeyran, Lucile Vanhersecke, Alban Bessede, Antoine Italiano
Anti-angiogenic agents elicit considerable immune modulatory effects within the tumor microenvironment, underscoring the rationale for synergistic clinical development of VEGF and immune checkpoint inhibitors in advanced gastric cancer (AGC). Early phase studies involving Asian patients demonstrated encouraging anti-tumor efficacies. We report the results of the REGOMUNE phase II study, in which Caucasian
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Discovery of vitexin as a novel VDR agonist that mitigates the transition from chronic intestinal inflammation to colorectal cancer Mol. Cancer (IF 27.7) Pub Date : 2024-09-13 Yonger Chen, Jian Liang, Shuxian Chen, Nan Lin, Shuoxi Xu, Jindian Miao, Jing Zhang, Chen Chen, Xin Yuan, Zhuoya Xie, Enlin Zhu, Mingsheng Cai, Xiaoli Wei, Shaozhen Hou, Hailin Tang
Colitis-associated colorectal cancer (CAC) frequently develops in patients with inflammatory bowel disease (IBD) who have been exposed to a prolonged state of chronic inflammation. The investigation of pharmacological agents and their mechanisms to prevent precancerous lesions and inhibit their progression remains a significant focus and challenge in CAC research. Previous studies have demonstrated
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Trem2-expressing multinucleated giant macrophages are a biomarker of good prognosis in head and neck squamous cell carcinoma Cancer Discov. (IF 29.7) Pub Date : 2024-09-13 Gregoire Gessain, Ahmed-Amine Anzali, Marvin Lerousseau, Kevin Mulder, Mathilde Bied, Anne Auperin, Daniel Stockholm, Nicolas Signolle, Farah Sassi, Maria Eugenia Marques Da Costa, Antonin Marchais, Alexandre Sayadi, Daniela Weidner, Stefan Uderhardt, Quentin Blampey, Sumanth Reddy Nakkireddy, Sophie Broutin, Charles-Antoine Dutertre, Pierre Busson, Thomas Walter, Alix Marhic, Antoine Moya-Plana, Joanne
Patients with head and neck squamous cell carcinomas (HNSCC) often have poor outcomes due to suboptimal risk-management and treatment strategies; yet integrating novel prognostic biomarkers into clinical practice is challenging. Here, we report the presence of multinucleated giant cells (MGC) – a type of macrophages – in tumors from patients with HNSCC, which are associated with a favorable prognosis
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NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations Cancer Discov. (IF 29.7) Pub Date : 2024-09-13 Jessica J. Lin, Joshua C. Horan, Anupong Tangpeerachaikul, Aurélie Swalduz, Augusto Valdivia, Melissa L. Johnson, Benjamin Besse, D. Ross Camidge, Toshio Fujino, Satoshi Yoda, Linh Nguyen-Phuong, Hayato Mizuta, Ludovic Bigot, Catline Nobre, Jii Bum Lee, Mi Ra Yu, Scot Mente, Yuting Sun, Nancy E. Kohl, James R. Porter, Matthew D. Shair, Viola W. Zhu, Enriqueta Felip, Byoung Chul Cho, Luc Friboulet,
Three generations of tyrosine kinase inhibitors (TKI) have been approved for anaplastic lymphoma kinase (ALK) fusion–positive non–small cell lung cancer. However, none address the combined need for broad resistance coverage, brain activity, and avoidance of clinically dose-limiting TRK inhibition. NVL-655 is a rationally designed TKI with >50-fold selectivity for ALK over 96% of the kinome tested.
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Epigenome reprogramming through H3K27 and H3K4 trimethylation as a resistance mechanism to DNA methylation inhibition in BRAFV600E-mutated colorectal cancer. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-13 Hey Min Lee, Ajay Kumar. Saw, Van K. Morris, Stefania Napolitano, Christopher Bristow, Sanjana Srinivasan, Michael Peoples, Alexey Sorokin, Preeti Kanikarla Marie, Jonathan Schulz, Anand K. Singh, Christopher Terranova, Oluwadara Coker, Abhinav Jain, Scott Kopetz, Kunal Rai
Purpose: BRAFV600E-mutated colorectal cancer (CRC) exhibits a strong correlation with DNA hypermethylation suggesting this subgroup of tumors presents unique epigenomic phenotypes. Nonetheless, 5-azacitidine, which inhibits DNA methyltransferase activity, is not efficacious in BRAFV600E CRC in vivo. Experimental Design: We randomized and treated mice implanted with patient-derived tumor xenografts
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MEK inhibitors lead to PDGFR pathway upregulation and sensitize tumors to RAF dimer inhibitors in NF1-deficient malignant peripheral nerve sheath tumor (MPNST) Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-13 Miguel A. Miranda-Román, Cindy J. Lee, Eve Fishinevich, Leili Ran, Amish J. Patel, Juan Yan, Makhzuna N. Khudoynazarova, Sarah Warda, Mohini R. Pachai, Yu Chen, Ping Chi
Purpose: Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive subtype of soft tissue sarcoma with a high propensity to metastasize and extremely limited treatment options. Loss of the RAS-GAP NF1 leads to sustained RAF/MEK/ERK signaling in MPNST. However, single-agent MEK inhibitors (MEKi) have failed to elicit a sustained inhibition of the MAPK signaling pathway in MPNST. Experimental
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Plasma ctDNA as a treatment response biomarker in metastatic cancers: evaluation by the RECIST working group Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-13 Alexander W. Wyatt, Saskia Litière, Francois-Clement Bidard, Luc Cabel, Lars Dyrskjøt, Chris A. Karlovich, Klaus Pantel, Joan Petrie, Reena Philip, Hillary S. Andrews, Paz J. Vellanki, Sofie H. Tolmeijer, Xenia Villalobos Alberu, Christian Alfano, Jan Bogaerts, Emiliano Calvo, Alice P. Chen, Rodrigo A. Toledo, Elisabeth G. E. de Vries, Lesley Seymour, Scott A. Laurie, Elena Garralda
Early indicators of metastatic cancer response to therapy are important for evaluating new drugs and stopping ineffective treatment. The Response Evaluation Criteria in Solid Tumors (RECIST) based on repeat cancer imaging are widely adopted in clinical trials, are used to identify active regimens that may change practice, and contribute to regulatory approvals. However, these criteria do not provide
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Androgen Deprivation Therapy Drives a Distinct Immune Phenotype in Localized Prostate Cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-13 Matthew C. Dallos, Aleksandar Z. Obradovic, Patrick McCann, Nivedita Chowdhury, Aditya Pratapa, David H. Aggen, Christopher Gaffney, Karen A. Autio, Renu K. Virk, Angelo M. De Marzo, Emmanuel S. Antonarakis, Howard I. Scher, Charles G. Drake, Dana E. Rathkopf
Purpose: Androgen deprivation therapy (ADT) remains the backbone of prostate cancer treatment. Beyond suppression of testosterone and tumor cell growth, emerging evidence suggests ADT also modulates the immune tumor microenvironment (TME). However, a more precise understanding of the timing and intricacies of these immunological shifts is needed. Experimental Design: Here we analyzed 49 primary prostate
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Health Insurance Continuity and Mortality in Children and Adolescents/Young Adults with Blood Cancer J. Natl. Cancer Inst. (IF 9.9) Pub Date : 2024-09-13 Xu Ji, Xinyue (Elyse) Zhang, K Robin Yabroff, Wendy Stock, Patricia Cornwell, Shasha Bai, Ann C Mertens, Joseph Lipscomb, Sharon M Castellino
Background Many uninsured patients do not receive Medicaid coverage until a cancer diagnosis, potentially delaying access to care for early cancer detection and treatment. We examine the association of Medicaid enrollment timing and patterns with survival among children and adolescents/young adults (AYAs) diagnosed with blood cancers, where disease onset can be acute and early detection is critical
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Increasing power in screening trials by testing control-arm specimens: application to multicancer detection screening J. Natl. Cancer Inst. (IF 9.9) Pub Date : 2024-09-13 Hormuzd A Katki, Philip C Prorok, Philip E Castle, Lori M Minasian, Paul F Pinsky
Background Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the “intended effect” (IE) analysis that we explain in detail herein. The IE analysis is particularly
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Ovarian cancer metastasis: Looking beyond the surface Cancer Cell (IF 48.8) Pub Date : 2024-09-12 Emine Bayraktar, Sisy Chen, Sara Corvigno, Jinsong Liu, Anil K. Sood
Historically, ovarian cancer (OC) was thought to metastasize by surface-to-surface spread, but recent developments have yielded a new understanding of the paths of metastatic spread. Given the histologic and molecular heterogeneity of OC, we will focus on high-grade serous carcinoma (HGSC). Here, we provide a critical and more holistic view of the evidence supporting various routes of metastasis, including
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From backstage to the spotlight: γδT cells in cancer Cancer Cell (IF 48.8) Pub Date : 2024-09-12 Robert Wiesheu, Seth B. Coffelt
γδT cells represent a group of immune cells that are understudied but whose utility has been recognized for cancer immunotherapy purposes. Recent studies have highlighted a critical role for these cells in tumor initiation, growth, and metastasis and revealed an increasingly complex biology of γδT cell subsets that is context and tissue specific. We discuss here how γδT cell subsets are regulated,
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Distinct tumor architectures and microenvironments for the initiation of breast cancer metastasis in the brain Cancer Cell (IF 48.8) Pub Date : 2024-09-12 Siting Gan, Danilo G. Macalinao, Sayyed Hamed Shahoei, Lin Tian, Xin Jin, Harihar Basnet, Catherine Bibby, James T. Muller, Pranita Atri, Evan Seffar, Walid Chatila, Ali Karacay, Pharto Chanda, Anna-Katerina Hadjantonakis, Nikolaus Schultz, Edi Brogi, Tejus A. Bale, Nelson S. Moss, Rajmohan Murali, Dana Pe’er, Joan Massagué
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Vorasidenib: a new hope or a false promise for patients with low-grade glioma? Nat. Rev. Clin. Oncol. (IF 81.1) Pub Date : 2024-09-12 Stanislav Lazarev, Kunal K. Sindhu
Despite recent FDA approval, the clinical utility of vorasidenib in the treatment of IDH-mutant low-grade gliomas remains unclear. Herein, we critique the pivotal trial of vorasidenib, and highlight the questionable choice of control intervention and end points, ethical concerns, as well as the uncertain efficacy observed, and argue that the approval might be premature given the high cost of this drug
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Correction: Identification of miPEP133 as a novel tumor-suppressor microprotein encoded by miR-34a pri-miRNA Mol. Cancer (IF 27.7) Pub Date : 2024-09-12 Min Kang, Bo Tang, Jixi Li, Ziyan Zhou, Kang Liu, Rensheng Wang, Ziyan Jiang, Fangfang Bi, David Patrick, Dongin Kim, Anirban K. Mitra, Yang Yang-Hartwich
Correction: Mol Cancer 19, 143 (2020) https://doi.org/10.1186/s12943-020-01248-9 Recently in a re-examination of our previously published paper [1], “Identification of miPEP133 as a novel tumor-suppressor microprotein encoded by miR-34a pri-miRNA” [Molecular Cancer 19, article number 143 (2020)], we found two errors. The first error is that we presented the wrong primer sequences for GAPDH in the Supplemental
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Accrual to Radiotherapy Trials in the US-Pitfalls and Potential Solutions. JAMA Oncol. (IF 22.5) Pub Date : 2024-09-12 Nina N Sanford,William A Hall
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Heterogeneity of Residual Disease After Neoadjuvant Systemic Therapy in Breast Cancer JAMA Oncol. (IF 22.5) Pub Date : 2024-09-12 Paolo Tarantino, Gabriel Hortobagyi, Sara M. Tolaney, Elizabeth A. Mittendorf
ImportanceOver the past 2 decades, systemic therapy for early-stage breast cancer has gradually moved from the adjuvant to the neoadjuvant setting. Administration of systemic therapy before surgery leads to potential improvements in surgical outcomes and allows for the assessment of the pathologic response to treatment. For patients with residual disease (RD), 3 adjuvant strategies have been shown
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Molecular, Socioeconomic, and Clinical Factors Affecting Racial and Ethnic Disparities in Colorectal Cancer Survival JAMA Oncol. (IF 22.5) Pub Date : 2024-09-12 Mahmoud Yousef, Abdelrahman Yousef, Saikat Chowdhury, Mohammad M. Fanaeian, Mark Knafl, Jennifer Peterson, Mohammad Zeineddine, Kristin Alfaro, Fadl Zeineddine, Drew Goldstein, Nicholas Hornstein, Arvind Dasari, Ryan Huey, Benny Johnson, Victoria Higbie, Alisha Bent, Bryan Kee, Michael Lee, Maria Pia Morelli, Van Karlyle Morris, Daniel Halperin, Michael J. Overman, Christine Parseghian, Eduardo Vilar
ImportanceDisparity in overall survival (OS) and differences in the frequency of driver gene variants by race and ethnicity have been separately observed in patients with colorectal cancer; however, how these differences contribute to survival disparity is unknown.ObjectiveTo quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in overall
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Cervical Cancer Incidence in the US-Affiliated Pacific Islands JAMA Oncol. (IF 22.5) Pub Date : 2024-09-12 Sameer V. Gopalani, Jin Qin, Janos Baksa, Trevor D. Thompson, Mona Saraiya, Virginia Senkomago, Paran Pordell, Youngju Jeong, Neal A. Palafox, Martina Reichhardt, Lee E. Buenconsejo-Lum
ImportanceThe World Health Organization has called for eliminating cervical cancer as a public health problem. Accurate and up-to-date estimates of population-based cervical cancer incidence are essential for monitoring progress toward elimination and informing local cancer control strategies, but these estimates are lacking for the US-Affiliated Pacific Islands (USAPI).ObjectiveTo calculate age-standardized
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Radiation-Associated Secondary Cancer in Patients With Breast Cancer Harboring TP53 Germline Variants JAMA Oncol. (IF 22.5) Pub Date : 2024-09-12 Gustav Y. Cederquist, Lillian A. Boe, Michael Walsh, Gary M. Freedman, Kara N. Maxwell, Neil Taunk, Lior Z. Braunstein
This cohort study examines the risk of radiation-associated sarcoma in patients with breast cancer harboring germline TP53 variants.
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Targeting Fatty Acid Metabolism Abrogates the Differentiation Blockade in Pre-leukemic Cells Cancer Res. (IF 12.5) Pub Date : 2024-09-12 Xiaoyu Liu, Yu Liu, Qing Rao, Yihan Mei, Haiyan Xing, Runxia Gu, Junli Mou, Manling Chen, Fan Ding, Wanqing Xie, Kejing Tang, Zheng Tian, Min Wang, Shaowei Qiu, Jianxiang Wang
Metabolism plays a key role in the maintenance of normal hematopoietic stem cells (HSCs) and in the development of leukemia. A better understanding of the metabolic characteristics and dependencies of pre-leukemic cells could help identify potential therapeutic targets to prevent leukemic transformation. As AML1-ETO, one of the most frequent fusion proteins in acute myeloid leukemia that is encoded
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Simultaneous Targeting of NQO1 and SOD1 Eradicates Breast Cancer Stem Cells via Mitochondrial Futile Redox Cycling Cancer Res. (IF 12.5) Pub Date : 2024-09-12 Ming Luo, Na Shen, Li Shang, Zeng Fang, Ying Xin, Yuxi Ma, Min Du, Yuan Yuan, Chenchen Hu, Yun Tang, Jing Huang, Wei Wei, Myung Ryul Lee, Paul J. Hergenrother, Max S. Wicha
Triple negative breast cancer (TNBC) contains the highest proportion of cancer stem-like cells (CSCs), which display intrinsic resistance to currently available cancer therapies. This therapeutic resistance is partially mediated by an antioxidant defense coordinated by the transcription factor NRF2 and its downstream targets including NQO1. Here, we identified the antioxidant enzymes NQO1 and SOD1
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Neuroendocrine Differentiation in Prostate Cancer Requires ASCL1 Cancer Res. (IF 12.5) Pub Date : 2024-09-12 Kathia E. Rodarte, Shaked Nir Heyman, Lei Guo, Lydia Flores, Trisha K. Savage, Juan Villarreal, Su Deng, Lin Xu, Rajal B. Shah, Trudy G. Oliver, Jane E. Johnson
Most patients with prostate adenocarcinoma develop resistance to therapies targeting the androgen receptor (AR). Consequently, a portion of these patients develop AR-independent neuroendocrine prostate cancer (NEPC), a rapidly progressing cancer with limited therapies and poor survival outcomes. Current research to understand the progression to NEPC suggests a model of lineage plasticity whereby AR-dependent
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Hepatocellular Carcinoma Immune Microenvironment Analysis: A Comprehensive Assessment with Computational and Classical Pathology Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-12 Caner Ercan, Salvatore Lorenzo. Renne, Luca Di Tommaso, Charlotte K.Y. Ng, Salvatore Piscuoglio, Luigi M. Terracciano
Purpose: The spatial variability and clinical relevance of the tumour immune microenvironment (TIME) are still poorly understood for hepatocellular carcinoma (HCC). Here we aim to develop a deep learning (DL)-based image analysis model for the spatial analysis of immune cell biomarkers, and microscopically evaluate the distribution of immune infiltration. Experimental Design: Ninety-two HCC surgical
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The Epstein-Barr virus nuclear antigen 1 variant associated with nasopharyngeal carcinoma defines the sequence criteria for serologic risk prediction Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-12 Benjamin E. Warner, Japan Patel, Renwei Wang, Jennifer Adams-Haduch, Yu-Tang Gao, Woon-Puay Koh, Ka Wo Wong, Alan K.S. Chiang, Jian-Min Yuan, Kathy H. Y. Shair
Purpose: Antibodies to select Epstein-Barr virus (EBV) proteins can diagnose early-stage nasopharyngeal carcinoma (NPC). We have previously shown that IgA against EBV nuclear antigen 1 (EBNA1) can predict incident NPC in high- and intermediate-risk cohorts 4 years pre-diagnosis. Here, we tested EBNA1 variants, with mutants, to define the sequence requirements for an NPC risk assay. Design: Mammalian-expressed
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TAK1 Promotes an Immunosuppressive Tumor Microenvironment through Cancer-Associated Fibroblast Phenotypic Conversion in Pancreatic Ductal Adenocarcinoma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-12 Nan Sheng, Koji Shindo, Kenoki Ohuchida, Tomohiko Shinkawa, Bo Zhang, Haimin Feng, Takeo Yamamoto, Taiki Moriyama, Naoki Ikenaga, Kohei Nakata, Yoshinao Oda, Masafumi Nakamura
Purpose: We aim to clarify the precise function of Transformed growth factor-beta 1 activated kinase-1 (TAK1) in cancer-associated fibroblasts (CAFs) within human pancreatic ductal adenocarcinoma (PDAC) by investigating its role in cytokine-mediated signaling pathways. Experimental Design: The expression of TAK1 in pancreatic cancer was confirmed by TCGA data and human pancreatic cancer specimens.
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A first-in-human phase 1 study of BXQ-350, a first-in-class sphingolipid metabolism regulator, in patients with advanced/recurrent solid tumors or high-grade gliomas Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-12 Olivier Rixe, John L. Villano, Robert Wesolowski, Anne M. Noonan, Vinay K. Puduvalli, Trisha M. Wise-Draper, Richard Curry, Emrullah Yilmaz, Charlie Cruze, Besim Ogretmen, Gilles Tapolsky, Ray Takigiku
Purpose: BXQ-350, a nanovesicle formulation of Saposin C, is an allosteric sphingolipid metabolism regulator that increases pro-apoptotic ceramide and decreases oncogenic sphingosine-1-phosphate (S1P) levels. We conducted a first-in-human, phase 1 study of BXQ-350. Patients and Methods: Adults (≥18 years old) with advanced/recurrent, treatment-refractory solid tumors or high-grade gliomas received