-
Evolving insights into the improvement of adoptive T-cell immunotherapy through PD-1/PD-L1 blockade in the clinical spectrum of lung cancer Mol. Cancer (IF 37.3) Pub Date : 2024-04-24 Yutao Li, Amit Sharma, Ingo G.H. Schmidt-Wolf
Undeniably, cancer immunotherapies have expanded the spectrum of cancer treatment, however, some patients do not respond to immunotherapies. This scenario is no different for lung cancer, whose two main types, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), still pose a serious clinical challenge. Adoptive T-cell therapies (ATC), which primarily include cytokine-induced killer
-
Co-transcriptional R-loops-mediated epigenetic regulation drives growth retardation and docetaxel chemosensitivity enhancement in advanced prostate cancer Mol. Cancer (IF 37.3) Pub Date : 2024-04-24 Yufan Ying, Yuqing Wu, Fenghao Zhang, Yijie Tang, Jiahe Yi, Xueyou Ma, Jiangfeng Li, Danni Chen, Xiao Wang, Xiaoyan Liu, Ben Liu, Jindan Luo, Xiangyi Zheng, Liping Xie
R-loops are prevalent three-stranded nucleic acid structures, comprising a DNA-RNA hybrid and a displaced single-stranded DNA, that frequently form during transcription and may be attributed to genomic stability and gene expression regulation. It was recently discovered that RNA modification contributes to maintain the stability of R-loops such as N6-methyladenosine (m6A). Yet, m6A-modified R-loops
-
Trans-Ancestral Genetic Risk Factors for Treatment-Related Type 2 Diabetes Mellitus in Survivors of Childhood Cancer J. Clin. Oncol. (IF 45.3) Pub Date : 2024-04-23 Cindy Im, Achal Neupane, Jessica L. Baedke, Brian Lenny, Angela Delaney, Stephanie B. Dixon, Eric J. Chow, Sogol Mostoufi-Moab, Tianzhong Yang, Melissa A. Richard, M. Monica Gramatges, Philip J. Lupo, Noha Sharafeldin, Smita Bhatia, Gregory T. Armstrong, Melissa M. Hudson, Kirsten K. Ness, Leslie L. Robison, Yutaka Yasui, Carmen L. Wilson, Yadav Sapkota
Journal of Clinical Oncology, Ahead of Print.
-
Datopotamab Deruxtecan in Advanced or Metastatic HR+/HER2– and Triple-Negative Breast Cancer: Results From the Phase I TROPION-PanTumor01 Study J. Clin. Oncol. (IF 45.3) Pub Date : 2024-04-23 Aditya Bardia, Ian E. Krop, Takahiro Kogawa, Dejan Juric, Anthony W. Tolcher, Erika P. Hamilton, Toru Mukohara, Aaron Lisberg, Toshio Shimizu, Alexander I. Spira, Junji Tsurutani, Senthil Damodaran, Kyriakos P. Papadopoulos, Jonathan Greenberg, Fumiaki Kobayashi, Hong Zebger-Gong, Rie Wong, Yui Kawasaki, Tadakatsu Nakamura, Funda Meric-Bernstam
Journal of Clinical Oncology, Ahead of Print.
-
Salvage Reirradiation for Locally Recurrent Prostate Cancer: Results From a Prospective Study With 7.2 Years of Follow-Up J. Clin. Oncol. (IF 45.3) Pub Date : 2024-04-23 Christian Ekanger, Svein Inge Helle, Lars Reisæter, Liv Bolstad Hysing, Rune Kvåle, Alfred Honoré, Karsten Gravdal, Sara Pilskog, Olav Dahl
Journal of Clinical Oncology, Ahead of Print.
-
Fraction dose escalation of hypofractionated radiotherapy with concurrent chemotherapy and subsequent consolidation immunotherapy in locally advanced non-small cell lung cancer: a phase 1 study Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Rui Zhou, FangJie Liu, HongMei Zhang, DaQuan Wang, PengXin Zhang, ShiYang Zheng, YiMei Liu, Li Chen, JinYu Guo, YingYi Zou, Yu-Ming Rong, Hui Liu, Bo Qiu
Purpose: This phase 1 trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer (LA-NSCLC). Patients and Methods: Split-course hypo-RT and hypo-boost combined with concurrent chemotherapy
-
Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized Actionable Pathways Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Mario E. Lacouture, Elena Goleva, Neil Shah, Veronica Rotemberg, Lukas Kraehenbuehl, Kwami F. Ketosugbo, Taha Merghoub, Tara Maier, Alexander Bang, Stephanie Gu, Trina Salvador, Andrea P. Moy, Taras Lyubchenko, Olivia Xiao, Clifton F. Hall, Evgeny Berdyshev, James Crooks, Ryan Weight, Jeffrey A. Kern, Donald Y.M. Leung
Purpose: Immune-related cutaneous adverse events (ircAEs) occur in ≥50% of patients treated with checkpoint inhibitors (CPI), but mechanisms are poorly understood. Experimental Design: Phenotyping/biomarker analyses were conducted in 200 patients on CPIs (139 with ircAEs, 61 without, control) to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies
-
FLT3 agonists and secondary hematopoietic malignancies: a potential class effect Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Henry W. Raeder, Michael W. Drazer
Expansion of cDC cells via FLT3 agonism has promising therapeutic potential in the treatment of advanced solid tumors. Here, we discuss the results of a clinical trial using GS-3583, an FLT3 agonist, that was stopped after a patient in the study developed acute myeloid leukemia.
-
Classifying glioma via liquid biopsy--progress towards an unmet clinical need Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Kalil G. Abdullah
The diagnosis and classification of glioma by liquid biopsy represents a critical unmet need in neuro oncology. A recent study demonstrates targeted next generation sequencing (NGS) of cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) as an evolving option for liquid biopsy in patients with glioma.
-
A First-in-Human Phase 1 Study of a Tumor-Directed RNA-Interference Drug against HIF2α in Patients with Advanced Clear Cell Renal Cell Carcinoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 James Brugarolas, Gregory Obara, Kathryn E. Beckermann, Brian Rini, Elaine T. Lam, James Hamilton, Thomas Schluep, Min Yi, So Wong, Zhongping Lily Mao, Erick Gamelin, Nizar M. Tannir
Purpose: ARO-HIF2 is an siRNA drug designed to selectively target hypoxia-inducible factor-2α (HIF2α) interrupting downstream pro-oncogenic signaling in clear cell renal cell carcinoma (ccRCC). The aims of this Phase 1 study (AROHIF21001) were to evaluate safety, tolerability, pharmacokinetics, and establish a recommended Phase 2 dose. Patients and Methods: Subjects with ccRCC and progressive disease
-
Genomic Profiling to Contextualize the Results of Intervention for Smoldering Multiple Myeloma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Dickran Kazandjian, Benjamin Diamond, Marios Papadimitriou, Elizabeth Hill, Romanos Sklavenitis-Pistofidis, Bachisio Ziccheddu, Patrick Blaney, Monika Chojnacka, Michael Durante, Kylee Maclachlan, Ryan Young, Saad Usmani, Faith Davies, Gad Getz, Irene Ghobrial, Neha Korde, Gareth Morgan, Francesco Maura, Ola Landgren
PURPOSE: Early intervention for High-Risk Smoldering Multiple Myeloma (HR-SMM) achieves deep and prolonged responses. It is unclear if beneficial outcomes are due to treatment of less complex, susceptible disease or inaccuracy in clinical definition of cases entered. EXPERIMENTAL DESIGN: Here, we interrogated whole genome and whole exome sequencing for 54 patients across two HR-SMM interventional studies
-
Overtreatment of multiple myeloma and its precursor states: de-escalation is an urgent need in clinical practice and trials Nat. Rev. Clin. Oncol. (IF 78.8) Pub Date : 2024-04-22 Ghulam Rehman Mohyuddin, Aaron M. Goodman
Certain subsets of patients with multiple myeloma or its precursor conditions are overtreated with current approaches to therapy. Herein, we highlight several key areas where we believe de-escalation of treatment is needed. Dedicated trials to assess these de-escalation approaches and urgent changes to current clinical practices are needed.
-
Investigating immune cells across time in vivo Nat. Rev. Cancer (IF 78.5) Pub Date : 2024-04-22 Daniel Kirschenbaum
In this Tools of the Trade article, Daniel Kirschenbaum describes the development of Zman-seq and its utility for capturing dynamic changes in cellular state within single-cell RNA sequencing data.
-
Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization Cancer Cell (IF 50.3) Pub Date : 2024-04-18 Wenying Wang, Tianran Li, Yue Cheng, Fei Li, Shuhong Qi, Min Mao, Jingjing Wu, Qing Liu, Xiaoning Zhang, Xuegang Li, Lu Zhang, Haoyue Qi, Lan Yang, Kaidi Yang, Zhicheng He, Shuaishuai Ding, Zhongyi Qin, Ying Yang, Xi Yang, Chunhua Luo, Yu Shi
-
Multiparametric MRI for characterization of the tumour microenvironment Nat. Rev. Clin. Oncol. (IF 78.8) Pub Date : 2024-04-19 Emily Hoffmann, Max Masthoff, Wolfgang G. Kunz, Max Seidensticker, Stefanie Bobe, Mirjam Gerwing, Wolfgang E. Berdel, Christoph Schliemann, Cornelius Faber, Moritz Wildgruber
-
Trametinib sensitizes KRAS-mutant lung adenocarcinoma tumors to PD-1/PD-L1 axis blockade via Id1 downregulation Mol. Cancer (IF 37.3) Pub Date : 2024-04-20 Ander Puyalto, María Rodríguez-Remírez, Inés López, Irati Macaya, Elizabeth Guruceaga, María Olmedo, Anna Vilalta-Lacarra, Connor Welch, Sergio Sandiego, Silvestre Vicent, Karmele Valencia, Alfonso Calvo, Ruben Pio, Luis E. Raez, Christian Rolfo, Daniel Ajona, Ignacio Gil-Bazo
The identification of novel therapeutic strategies to overcome resistance to the MEK inhibitor trametinib in mutant KRAS lung adenocarcinoma (LUAD) is a challenge. This study analyzes the effects of trametinib on Id1 protein, a key factor involved in the KRAS oncogenic pathway, and investigates the role of Id1 in the acquired resistance to trametinib as well as the synergistic anticancer effect of
-
Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial J. Clin. Oncol. (IF 45.3) Pub Date : 2024-04-19 Robert S. Fichtinger, Luca A. Aldrighetti, Mohammed Abu Hilal, Roberto I. Troisi, Robert P. Sutcliffe, Marc G. Besselink, Somaiah Aroori, Krishna V. Menon, Bjørn Edwin, Mathieu D'Hondt, Valerio Lucidi, Tom F. Ulmer, Rafael Díaz-Nieto, Zahir Soonawalla, Steve White, Gregory Sergeant, Bram Olij, Francesca Ratti, Christoph Kuemmerli, Vincenzo Scuderi, Frederik Berrevoet, Aude Vanlander, Ravi Marudanayagam
Journal of Clinical Oncology, Ahead of Print.
-
A Machine Learning Algorithm Facilitates Prognosis Prediction and Treatment Selection for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-19 Ji Won Han, Soon Kyu Lee, Jung Hyun Kwon, Soon Woo Nam, Hyun Yang, Si Hyun Bae, Ji Hoon Kim, Heechul Nam, Chang Wook Kim, Hae Lim Lee, Hee Yeon Kim, Sung Won Lee, Ahlim Lee, U Im Chang, Do Seon Song, Seok-Hwan Kim, Myeong Jun Song, Pil Soo Sung, Jong Young Choi, Seung Kew Yoon, Jeong Won Jang
Background: Given its heterogeneity and diverse clinical outcomes, precise subclassification of BCLC-C hepatocellular carcinoma (HCC) is required for appropriately determining patient prognosis and selecting treatment. Methods: We recruited 2,626 patients with BCLC-C stage HCC from multiple centers, comprising training/test (n=1,693) and validation cohorts (n=933). The XGBoost was chosen for maximum
-
A Cohort Study to Evaluate Genetic Predictors for Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS): Results from ECOG-ACRIN E1Z11 Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-19 Vered Stearns, Opeyemi A. Jegede, Victor Tsu-Shih. Chang, Todd C. Skaar, Jeffrey L. Berenberg, Ranveer Nand, Atif Shafqat, Nisha Lassi. Jacobs, William Luginbuhl, Paul Gilman, Al B. Benson, Judie R. Goodman, Gary L. Buchschacher, N. Lynn. Henry, Charles L. Loprinzi, Patrick J. Flynn, Edith P. Mitchell, Michael Jordan. Fisch, Joseph A. Sparano, Lynne I. Wagner
Purpose: Aromatase Inhibitor-Associated Musculoskeletal Symptoms (AIMSS) are common and frequently lead to AI discontinuation. Single nucleotide polymorphisms (SNPs) in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate associations between 10 SNPs and AI discontinuation due to AIMSS. Patients and Methods: Postmenopausal
-
Integrating multisector molecular characterization into personalized peptide vaccine design for patients with newly diagnosed glioblastoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-19 Tanner M. Johanns, Elizabeth A.R. Garfinkle, Katherine E. Miller, Alexandra J. Livingstone, Kaleigh F. Roberts, Lakshmi Prakruthi Rao Venkata, Joshua L. Dowling, Michael R. Chicoine, Ralph G. Dacey, Gregory J. Zipfel, Albert H. Kim, Elaine R. Mardis, Gavin P. Dunn
Purpose: Glioblastoma (GBM) patient outcomes remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits
-
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
-
Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-04-19 Da-Feng Lin, Hai-Lin Li, Ting Liu, Xiao-Fei Lv, Chuan-Miao Xie, Xiao-Min Ou, Jian Guan, Ye Zhang, Wen-Bin Yan, Mei-Lin He, Meng-Yuan Mao, Xun Zhao, Lian-Zhen Zhong, Wen-Hui Chen, Qiu-Yan Chen, Hai-Qiang Mai, Rou-Jun Peng, Jie Tian, Lin-Quan Tang, Di Dong
Background The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma (lrNPC) is limited due to their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in lrNPC. Methods This multicenter, retrospective study included 921 patients with lrNPC. A machine learning
-
ALND can be safely omitted for patients with sentinel-node macrometastases Nat. Rev. Clin. Oncol. (IF 78.8) Pub Date : 2024-04-18 David Killock
Omission of completion axillary lymph-node dissection (ALND) has been shown to mitigate lymphoedema without compromising survival outcomes in patients with clinically node-negative (cN0) breast cancer who have nodal metastasis detected upon sentinel lymph-node biopsy (SLNB), albeit in trials with limited statistical power and clinical representativeness. Now, data from the phase III SENOMAC trial in
-
Afami-cel provides a novel treatment option for rare sarcoma subtypes Nat. Rev. Clin. Oncol. (IF 78.8) Pub Date : 2024-04-18 Peter Sidaway
Patients with metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma (comprising 5–10% of all soft-tissue sarcomas) typically have limited long-term survival, especially after disease recurrence on first-line therapy. Now, data from the phase II SPEARHEAD-1 trial testing afamitresgene autoleucel (afami-cel), a CD4+ and CD8+ T cell product transduced with an affinity-enhanced MAGE-A4-specific
-
T-Cell Malignant Neoplasms After Chimeric Antigen Receptor T-Cell Therapy JAMA Oncol. (IF 28.4) Pub Date : 2024-04-18 Ryan Storgard, Kai Rejeski, Miguel-Angel Perales, Adam Goldman, Roni Shouval
This cohort study assesses the increase in second primary malignant neoplasms and T-cell malignant neoplasm cases associated with chimeric antigen receptor–T cells.
-
Policy Priorities in Cancer Care for Transgender People JAMA Oncol. (IF 28.4) Pub Date : 2024-04-18 Alicia C. Smart, Michael J. Yunes, Karen M. Winkfield
This Viewpoint calls for health care systems, oncologists, and staff to prioritize and adopt policies that are inclusive and respectful of transgender patients with cancer.
-
Adherence to American Cancer Society Nutrition and Physical Activity Guidelines Among Cancer Survivors JAMA Oncol. (IF 28.4) Pub Date : 2024-04-18 Carter Baughman, Kathryn Norman, Kenneth Mukamal
ImportanceThe American Cancer Society’s (ACS’s) nutrition and physical activity guidelines are intended to reduce morbidity and mortality among cancer survivors, but to our knowledge, adherence to these guidelines has not been systematically quantified.ObjectiveTo evaluate adherence to and factors associated with adherence to lifestyle modification guidelines among cancer survivors.Design, Setting
-
Allogeneic CD19/CD22 CAR T-Cell Therapy for B-Cell Acute Lymphoblastic Leukemia JAMA Oncol. (IF 28.4) Pub Date : 2024-04-18 Laurent Phely, Luca Hensen, Christoph Faul, Christer Alexander Ruff, Dina Schneider, Wolfgang Andreas Bethge, Claudia Lengerke
This case series reports durable remissions in 2 patients with relapsed/refractory B-cell acute lymphoblastic leukemia treated with allogeneic bispecific CD19/CD22-targeting chimeric antigen receptor T cells.
-
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
-
Systematic investigation of genetically determined plasma and urinary metabolites to discover potential interventional targets for colorectal cancer J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-04-18 Jing Sun, Jianhui Zhao, Siyun Zhou, Xinxuan Li, Tengfei Li, Lijuan Wang, Shuai Yuan, Dong Chen, Philip J Law, Susanna C Larsson, Susan M Farrington, Richard S Houlston, Malcolm G Dunlop, Evropi Theodoratou, Xue Li
Background We aimed to identify plasma and urinary metabolites related to colorectal cancer (CRC) risk and elucidate their mediator role in the associations between modifiable risk factors and CRC. Methods Metabolite quantitative trait loci were derived from two published metabolomics genome-wide association studies (GWASs), and summary-level data were extracted for 651 plasma metabolites and 208 urinary
-
Low-dose ionizing γ-radiation elicits the extrusion of neutrophil extracellular traps Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Alvaro Teijeira, Saray Garasa, Maria C. Ochoa, Sandra Sanchez-Gregorio, Gabriel Gomis, Carlos Luri-Rey, Rafael Martinez-Monge, Beatrice Pinci, Karmele Valencia, Belen Palencia, Benigno Barbes, Elixabet Bolanos, Arantza Azpilikueta, Marina Garcia-Cardosa, Javier Burguete, Iñaki Eguren-Santamaria, Eneko Garate-Soraluze, Pedro Berraondo, Jose L. Perez-Gracia, Carlos E. de Andrea, Maria E. Rodriguez-Ruiz
Purpose: Cancer patients frequently undergo radiotherapy in their clinical management with unintended irradiation of blood vessels and copiously irrigated organs in which polymorphonuclear leukocytes circulate. Following the observation that such low doses of ionizing radiation are able to induce neutrophils to extrude neutrophil extracellular traps (NETs), we have investigated the mechanisms, consequences
-
Monitoring hepatocellular carcinoma using tumor content in circulating cell-free DNA Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Shifeng Lian, Chenyu Lu, Fugui Li, Xia Yu, Limei Ai, Biao-Hua Wu, Xueyi Gong, Wenjing Zhou, Xuejun Liang, Jiyun Zhan, Yong Yuan, Fang Fang, Zhiwei Liu, Mingfang Ji, Zongli Zheng
Purpose: To evaluate the utility of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history. Methods: We included 67 hepatitis B virus (HBV)-related HCC patients, of whom 17 had paired pre- and post-treatment samples, and 90 controls. Additionally, in a prospective cohort with HBV surface antigen-positive participants recruited
-
Facts and hopes on cancer immunotherapy for small cell lung cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Jon Zugazagoitia, Handerson Osma, Javier Baena, Álvaro C. Ucero, Luis Paz-Ares
Platinum-based chemotherapy plus PD-1 axis blockade is the standard of care in the front-line treatment of extensive-stage small cell lung cancer (ES-SCLC). Despite the robust and consistent increase of long-term survival with PD-1 axis inhibition, the magnitude of the benefit from immunotherapy appears lower as compared to other solid tumors. Several immune evasive mechanisms have been shown to be
-
Maintenance pembrolizumab therapy in patients with metastatic HER2-negative breast cancer with prior response to chemotherapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Toshiaki Iwase, Evan N. Cohen, Hui Gao, Angela Alexander, Megumi Kai, Vivian Chiv, Xiaoping Wang, Savitri Krishnamurthy, Diane Liu, Yu Shen, Kumiko Kida, Alexandre Reuben, Rachel Layman, David Ramirez, Debu Tripathy, Stacy L. Moulder, Clinton Yam, Vicente Valero, Bora Lim, James M. Reuben, Naoto T. Ueno
Purpose: Accumulating toxicities hinder indefinite chemotherapy for many patients with metastatic/recurrent HER2-negative breast cancer. We conducted a phase II trial of pembrolizumab monotherapy following induction chemotherapy to determine the efficacy of maintenance immunotherapy in patients with metastatic HER2-negative inflammatory breast cancer (IBC) and non-IBC triple-negative breast cancer
-
Spatially preserved multi-region transcriptomic subtyping and biomarkers of chemoimmunotherapy outcome in extensive-stage small cell lung cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Melina Peressini, Rosario Garcia-Campelo, Bartomeu Massuti, Cristina Marti, Manuel Cobo, Vanesa Gutiérrez, Manuel Dómine, Jose Fuentes, Margarita Majem, Javier de Castro, Juan Felipe Cordoba, Maria Pilar Diz, Dolores Isla, Emilio Esteban, Enric Carcereny, Laia Vila, Alberto Moreno-Vega, Silverio Ros, Amaia Moreno, Francisco Javier Garcia, Gerardo Huidobro, Carlos Aguado, Victor Cebey-Lopez, Javier
Background: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. Patients and methods: We analyzed tumor samples from 58 ES-SCLC patients enrolled in two multicenter single-arm
-
Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity from a Phase I Study of Simlukafusp Alfa (FAP-IL2v) in Advanced/Metastatic Solid Tumors Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Neeltje Steeghs, Carlos Gomez-Roca, Kristoffer S. Rohrberg, Morten Mau-Sørensen, Debbie Robbrecht, Josep Tabernero, Samreen Ahmed, Maria E. Rodriguez-Ruiz, Caroline Ardeshir, Daniela Schmid, Nassim Sleiman, Carl Watson, Hanna Piper-Lepoutre, David Dejardin, Stefan Evers, Christophe Boetsch, Jehad Charo, Volker Teichgräber, Ignacio Melero
Purpose: Simlukafusp alfa (FAP-IL2v), a tumor-targeted immunocytokine, comprising an interleukin-2 variant moiety with abolished CD25 binding fused to human immunoglobulin G1, is directed against fibroblast activation protein-α. This phase I, open-label, multicenter, dose-escalation and extension study (NCT02627274) evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of
-
Efficacy of pembrolizumab and biomarker analysis in patients with WGS-based intermediate to high tumor mutational load: results from the Drug Rediscovery Protocol Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Birgit S. Geurts, Laurien J. Zeverijn, Lindsay V.M. Leek, Jade M. van Berge Henegouwen, Louisa R. Hoes, Hanneke van der Wijngaart, Vincent van der Noort, Joris van de Haar, Annemiek van Ommen-Nijhof, Marleen Kok, Paul Roepman, Anne M.L. Jansen, Wendy W.J. de Leng, Maja J. A. de Jonge, Ann Hoeben, Carla M.L. van Herpen, Hans M. Westgeest, Lodewyk F.A. Wessels, Henk M.W. Verheul, Hans Gelderblom, Emile
Purpose: To evaluate efficacy of pembrolizumab across multiple cancer types harboring different levels of Whole-Genome Sequencing (WGS)-based tumor mutational load (TML; total of non-synonymous mutations across the genome) in patients included in the Drug Rediscovery Protocol (NCT02925234). Patients and methods: Patients with solid, treatment-refractory, microsatellite-stable tumors were enrolled in
-
Overcoming osimertinib resistance with AKT inhibition in EGFRm-driven Non-Small-Cell-Lung-Cancer with PIK3CA/PTEN alterations Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Ursula Grazini, Aleksandra Markovets, Lucy Ireland, Daniel O'Neill, Benjamin Phillips, Man Xu, Matthias Pfeifer, Tereza Vaclova, Matthew J. Martin, Ludovic Bigot, Luc Friboulet, Ryan Hartmaier, Maria Emanuela Cuomo, Simon T. Barry, Paul D. Smith, Nicolas Floc'h
Purpose: Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) indicated for the treatment of EGFR mutated (EGFRm)-driven lung adenocarcinomas. Osimertinib significantly improves progression-free survival in first-line treated patients with EGFRm advanced NSCLC. Despite the durable disease control, the majority of patients receiving osimertinib eventually develop disease
-
A cohort study of CNS tumors in Multiple Endocrine Neoplasia Type 1 Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Thomas Graillon, Pauline Romanet, Clara Camilla, Camille Gelin, Romain Appay, Catherine Roche, Arnaud Lagarde, Grégory Mougel, Kaissar Farah, Maëlle Le Bras, Julien Engelhardt, Michel Kalamarides, Matthieu Peyre, Aymeric Amelot, Evelyne Emery, Elsa Magro, Helene Cebula, Rabih Aboukais, Catherine Bauters, Emmanuel Jouanneau, Moncef Berhouma, Thomas Cuny, Henry Dufour, Hugues Loiseau, Dominique Figarella-Branger
Purpose: Multiple Endocrine Neoplasia Type-1 (MEN1) is thought to increase the risk of meningioma and ependymoma. Hereby, we aimed to describe the frequency, the incidence and specific clinical and histological features of CNS tumors in the MEN1 population (except pituitary tumors). Experimental design: The study population included patients harboring CNS tumors diagnosed with MEN1 syndrome after 1990
-
Diffuse pleural mesotheliomas with genomic near-haploidization: a newly recognized subset with distinct clinical, histologic, and molecular features Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Soo-Ryum Yang, Gowtham Jayakumaran, Jamal Benhamida, Christopher A. Febres Aldana, Rachel Fanaroff, Jason Chang, Erika Gedvilaite, Liliana B. Villafania, Jennifer L. Sauter, Michael Offin, Marjorie G. Zauderer, Marc Ladanyi
Purpose: Diffuse pleural mesotheliomas (DPMs) with genomic near-haploidization (GNH) represent a novel subtype first recognized by the TCGA project; however, its clinicopathologic and molecular features remain poorly defined. Experimental design: We analyzed clinical genomic profiling data from 290 patients with DPM using the MSK-IMPACT assay. Allele-specific copy number analysis was performed using
-
Not only a Western world issue: Cancer incidence in younger individuals in the United Arab Emirates CA: Cancer J. Clin. (IF 254.7) Pub Date : 2024-04-16 Humaid O. Al-Shamsi, Khaled M. Musallam
Two important reports regarding cancer incidence in the United States1 and globally2 have been recently released. In summary, almost 20 million people worldwide were diagnosed with cancer in 2022, and almost 10 million died of their disease.2 Lung cancer is the most common cancer globally, followed by female breast, colorectal, prostate, and stomach cancers. For women, breast cancer is the most common
-
Guardrails for the use of generalist AI in cancer care Nat. Rev. Cancer (IF 78.5) Pub Date : 2024-04-16 Stephen Gilbert, Jakob Nikolas Kather
-
Combinatorial strategies to target RAS-driven cancers Nat. Rev. Cancer (IF 78.5) Pub Date : 2024-04-16 Naiara Perurena, Lisa Situ, Karen Cichowski
-
Efficacy and safety of bispecific antibodies vs. immune checkpoint blockade combination therapy in cancer: a real-world comparison Mol. Cancer (IF 37.3) Pub Date : 2024-04-16 Linyan Cheng, Lujun Chen, Yuan Shi, Weiying Gu, Weidong Ding, Xiao Zheng, Yan Liu, Jingting Jiang, Zhuojun Zheng
Emerging tumor immunotherapy methods encompass bispecific antibodies (BSABs), immune checkpoint inhibitors (ICIs), and adoptive cell immunotherapy. BSABs belong to the antibody family that can specifically recognize two different antigens or epitopes on the same antigen. These antibodies demonstrate superior clinical efficacy than monoclonal antibodies, indicating their role as a promising tumor immunotherapy
-
Lighting the torch: intratumoural T cell-to-stroma enrichment score as a predictor of immunotherapy response in urothelial carcinoma Nat. Rev. Clin. Oncol. (IF 78.8) Pub Date : 2024-04-15 David H. Aggen, Jonathan E. Rosenberg
-
tRNA-derived small RNAs in human cancers: roles, mechanisms, and clinical application Mol. Cancer (IF 37.3) Pub Date : 2024-04-15 Manli Zhou, Xiaoyun He, Jing Zhang, Cheng Mei, Baiyun Zhong, Chunlin Ou
Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are a new type of non-coding RNAs (ncRNAs) produced by the specific cleavage of precursor or mature tRNAs. tsRNAs are involved in various basic biological processes such as epigenetic, transcriptional, post-transcriptional, and translation regulation, thereby affecting the occurrence and development of various human diseases, including cancers. Recent
-
Mutation Patterns Predict Drug Sensitivity in Acute Myeloid Leukemia Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-15 Guangrong Qin, Jin Dai, Sylvia Chien, Timothy J. Martins, Brenda Loera, Quy H. Nguyen, Melanie L. Oakes, Bahar Tercan, Boris Aguilar, Lauren Hagen, Jeannine McCune, Richard Gelinas, Raymond J. Monnat, Ilya Shmulevich, Pamela S. Becker
Purpose: The inherent genetic heterogeneity of acute myeloid leukemia (AML) has challenged the development of precise and effective therapies. The objective of this study was to elucidate the genomic basis of drug resistance or sensitivity, identify signatures for drug response prediction, and provide resources to the research community. Experimental Design: We performed targeted sequencing, high-throughput
-
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
-
Systematic Review of Cerebrospinal Fluid Biomarker Discovery in Neuro-Oncology: A Roadmap to Standardization and Clinical Application J. Clin. Oncol. (IF 45.3) Pub Date : 2024-04-12 Nicholas Mikolajewicz, Patricia P. Yee, Debarati Bhanja, Mara Trifoi, Alexandra M. Miller, Philippe Metellus, Stephen J. Bagley, Leonora Balaj, Leonardo J.M. de Macedo Filho, Brad E. Zacharia, Dawit Aregawi, Michael Glantz, Michael Weller, Manmeet S. Ahluwalia, Thomas Kislinger, Alireza Mansouri
Journal of Clinical Oncology, Ahead of Print.
-
A population-based study of COVID-19 mortality risk in US cancer patients J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-04-13 Kyle A Mani, Xue Wu, Daniel E Spratt, Ming Wang, Nicholas G Zaorsky
Background In this study, we provide the largest analysis to date of a US-based cancer cohort to characterize death from COVID-19. Methods A total of 4,020,669 patients across 15 subtypes living with cancer in 2020 and included in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database were abstracted. We investigated prognostic factors for death due to COVID-19
-
Programming immune escape Nat. Rev. Cancer (IF 78.5) Pub Date : 2024-04-12 Daniela Senft
In a recent study published in Nature, Goto et al. explore mechanisms of immune evasion in early colorectal cancers and adenomas and identify SOX17 to be crucial for immune escape through suppression of interferon-γ signalling.