Featured
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Correspondence |
A synthetic control arm for refractory metastatic colorectal cancer: the no placebo initiative
- Takayuki Yoshino
- , Qian Shi
- & Aimery de Gramont
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Article
| Open AccessMesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results
T cells containing an anti-mesothelin single-domain antibody fused to a component of the endogenous T cell receptor signaling complex exhibit notable toxicities but encouraging clinical responses in patients with treatment-refractory mesothelioma and ovarian cancer.
- Raffit Hassan
- , Marcus Butler
- & David Hong
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Brief Communication
| Open AccessA reinforcement learning model for AI-based decision support in skin cancer
A reinforcement learning model developed to adapt artificial intelligence (AI) predictions to human preferences showed better sensitivity for skin cancer diagnoses and improved management decisions compared to a supervised learning model.
- Catarina Barata
- , Veronica Rotemberg
- & Harald Kittler
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Comment |
Correcting the drug development paradigm for glioblastoma requires serial tissue sampling
A breakthrough in drug discovery for glioblastoma requires serial collection of tissue from the central nervous system via window of opportunity trials
- Kirit Singh
- , Kelly M. Hotchkiss
- & Mustafa Khasraw
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Article
| Open AccessTrastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial
Trastuzumab deruxtecan, an anti-HER2–drug conjugate, exhibits the highest objective response rate in patients with HER2-overexpressing metastatic breast cancer, but clinical activity is also observed in patients with HER2-low or non-expressing tumors, potentially pointing to additional determinants of drug efficacy.
- Fernanda Mosele
- , Elise Deluche
- & Fabrice André
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Article
| Open AccessNeoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial
In the NATION-1907 trial, treatment of patients with resectable esophageal squamous cell carcinoma with the anti-PD-L1 agent adebrelimab was safe and showed preliminary overall survival efficacy, with responders exhibiting an immune-enriched tumor microenvironment phenotype at baseline.
- Jun Yin
- , Jingnan Yuan
- & Qing Zhou
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Article |
First-line pyrotinib in advanced HER2-mutant non-small-cell lung cancer: a patient-centric phase 2 trial
Treatment of patients with HER2-mutant non-small-cell lung cancer with the pan-HER inhibitor pyrotinib in a phase 2 trial or compassionate use showed a favorable objective response rate, whereas patients treated in parallel by physician’s choice in a real-world study did not.
- Si-Yang Maggie Liu
- , Hai-Yan Tu
- & Yi-Long Wu
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Article |
Microbiome-derived cobalamin and succinyl-CoA as biomarkers for improved screening of anal cancer
Two products of the anal microbiome improve the specificity and sensitivity of diagnosing high-grade precursor lesions to anal cancer over cytology.
- Sergio Serrano-Villar
- , Camilla Tincati
- & Manuel Ferrer
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Article
| Open AccessTranscriptional signatures associated with persisting CD19 CAR-T cells in children with leukemia
In children with relapsed or refractory B cell acute lymphoblastic leukemia and in complete remission after CD19 CAR-T cell therapy, long-lived CAR-T cells express a persistence gene signature that is also present in persistent CD19 CAR-T cells from adults with chronic lymphocytic leukemia.
- Nathaniel D. Anderson
- , Jack Birch
- & Sara Ghorashian
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Article |
Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial
In patients with advanced melanoma, fecal microbiota transplantation from healthy donors combined with the anti-PD-1 inhibitors nivolumab or pembrolizumab was well tolerated with an encouraging objective response rate of 65% in the first-line treatment setting.
- Bertrand Routy
- , John G. Lenehan
- & Saman Maleki Vareki
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Article |
CD19 CAR T-cell therapy and prophylactic anakinra in relapsed or refractory lymphoma: phase 2 trial interim results
Prophylactic subcutaneous administration of anakinra, an IL-1 receptor inhibitor, reduced severe immune effector cell-associated neurotoxicity syndrome incidence in patients with relapsed or refractory large B-cell and mantle cell lymphoma treated with anti-CD19 chimeric antigen receptor (CAR) T cells.
- Jae H. Park
- , Karthik Nath
- & Michel Sadelain
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Research Highlight |
Base-edited CAR T cells for pediatric leukemia
Researchers used base editing — a type of CRISPR technology — to create a cell-therapy product with potent activity in children with relapsed T-ALL.
- Karen O’Leary
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Consensus Statement |
A joint international consensus statement for measuring quality of survival for patients with childhood cancer
The International Childhood Cancer Outcome Project group, involving survivors and other relevant stakeholders, develop a set of core outcomes to measure the quality of care for 17 types of childhood cancers.
- Rebecca J. van Kalsbeek
- , Melissa M. Hudson
- & Lisa Zwiers
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Perspective |
The NCI-MATCH trial: lessons for precision oncology
The recently completed NCI-MATCH is one of the largest precision oncology trials undertaken to date; this Perspective discusses key aspects of its design and conduct, and lessons for future precision oncology studies.
- Peter J. O’Dwyer
- , Robert J. Gray
- & James H. Doroshow
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Article |
Intratumoral dendritic cell–CD4+ T helper cell niches enable CD8+ T cell differentiation following PD-1 blockade in hepatocellular carcinoma
Response to anti-PD-1 in patients with hepatocellular carcinoma is associated with clonal expansion of intratumoral CXCL13+ CD4+ helper T cells and effector-like CD8+ T cells, and local dendritic cells enriched in expression of maturation and regulatory molecules help facilitate CD8+ T cell differentiation.
- Assaf Magen
- , Pauline Hamon
- & Miriam Merad
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Research Highlight |
A new targeted therapy for low-grade glioma
The dual IDH1–IDH2 inhibitor vorasidenib more than doubled time to progression (relative to placebo) and thus represents the first new treatment in decades for patients with glioma.
- Karen O’Leary
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Article |
The tumor immune microenvironment of nasopharyngeal carcinoma after gemcitabine plus cisplatin treatment
Analysis of tumor samples from patients with nasopharyngeal carcinoma shows that gemcitabine plus cisplatin chemotherapy activates a unique population of innate-like B cells, which enhance the cytotoxic CD8+ T cell response and are associated with better clinical outcomes.
- Jiawei Lv
- , Yuan Wei
- & Jun Ma
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Article
| Open AccessCamonsertib in DNA damage response-deficient advanced solid tumors: phase 1 trial results
In patients with DNA damage response-deficient solid tumors, the oral ATR kinase inhibitor camonsertib was well tolerated; a recommended phase 2 dose was identified; and encouraging anti-tumor activity was observed, with the highest response rate observed in patients with ovarian cancer.
- Timothy A. Yap
- , Elisa Fontana
- & Ezra Rosen
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Article |
Pembrolizumab in brain metastases of diverse histologies: phase 2 trial results
In a phase 2 trial of patients with untreated, recurrent and progressive brain metastases treated with an anti-programmed cell death protein 1 inhibitor, the overall intracranial benefit rate was 42.1%, which met the prespecified primary endpoint.
- Priscilla K. Brastianos
- , Albert E. Kim
- & Ryan J. Sullivan
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Article
| Open AccessGenetically adjusted PSA levels for prostate cancer screening
Analyses of large population-based cohorts and clinical trials show that using polygenic scores to account for variability in PSA levels improves detection of prostate cancer, suggesting an approach for enhancing screening accuracy.
- Linda Kachuri
- , Thomas J. Hoffmann
- & John S. Witte
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Research Briefing |
Stress response in tumor-infiltrating T cells is linked to immunotherapy resistance
A newly composed single-cell transcriptomic atlas of tumor-infiltrating T cells across 16 cancer types revealed previously undescribed T cell states and heterogeneity. A unique T cell stress response state, TSTR, was linked to immunotherapy resistance. Our high-resolution T cell reference maps, web portal, and annotation tool can assist efforts to develop T cell therapies.
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Resource |
Pan-cancer T cell atlas links a cellular stress response state to immunotherapy resistance
A single-cell analysis of tumor-infiltrating T cells from 16 cancer types identifies new T cell subsets and a stress response cell state enriched in tumors resistant to immunotherapy.
- Yanshuo Chu
- , Enyu Dai
- & Linghua Wang
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Research Highlight |
Navigating pregnancy and breast cancer
In a clinical trial, interrupting adjuvant endocrine therapy to attempt pregnancy did not increase the risk of breast cancer recurrence.
- Sonia Muliyil
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Resource
| Open AccessAn integrated tumor, immune and microbiome atlas of colon cancer
A large, publicly available dataset integrating RNA, whole-exome, T cell receptor and 16S rRNA sequencing from patients with colon cancer enables the discovery of a prognostic score consisting of tumor, immune and microbial features.
- Jessica Roelands
- , Peter J. K. Kuppen
- & Davide Bedognetti
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Research Briefing |
Immune–microbiota interactions affect the prognosis of patients with colon cancer
We characterized cancer cells, immune responses and the microbiota composition in a cohort of primary colon cancers. Multi-omic analyses defined parameters associated with favorable prognosis, including a score that captured the intratumoral immune response and a specific microbiome signature. This data repository (atlas and compass of immune–cancer–microbiome interactions (AC-ICAM)) is publicly available.
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Comment |
Neoadjuvant immunotherapy for melanoma is now ready for clinical practice
Individuals with cutaneous melanoma who are treated with neoadjuvant immunotherapy show a substantial improvement; this should be incorporated into standard care.
- Claus Garbe
- , Reinhard Dummer
- & Georgina V. Long
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News & Views |
Advancing combination therapy for recurrent glioblastoma
Adding an oncolytic virus to classic immune checkpoint inhibition elicits treatment responses and survival benefit for select immunologically ‘cold’ recurrent glioblastomas, although creative treatment strategies are still needed for patients with highly anti-inflammatory tumors.
- Adela Wu
- & Michael Lim
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Article |
Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: updated phase 1 trial interim results
In updated results from a phase 1 trial of GD2-specific CAR-NKT cells in patients with neuroblastoma, no dose-limiting toxicities were observed across multiple dose levels; the maximum tolerated dose was not reached; and there was evidence of anti-tumor activity.
- Andras Heczey
- , Xin Xu
- & Leonid S. Metelitsa
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Article
| Open AccessOncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial
A safety and efficacy trial of a single intratumoral dose of the oncolytic adenovirus DNX-2401 followed by intravenous anti-PD-1 pembrolizumab in patients with recurrent glioblastoma shows an encouraging clinical benefit rate and 12 months overall survival.
- Farshad Nassiri
- , Vikas Patil
- & Gelareh Zadeh
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Article
| Open AccessA deep learning algorithm to predict risk of pancreatic cancer from disease trajectories
A deep learning algorithm using electronic health records from two large cohorts of patients predicts the risk of pancreatic cancer from pre-cancer disease trajectories up to 3 years in advance, showing promising performance in retrospective validation.
- Davide Placido
- , Bo Yuan
- & Chris Sander
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News & Views |
A call to improve the quality of screening programs
The CanScreen5 project provides a tool for monitoring the performance and improving the quality of global cancer screening programs — and highlights the importance of robust quality assurance in this setting.
- Fei Wang
- , Xuesi Dong
- & Ni Li
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Article
| Open AccessMulti-organ landscape of therapy-resistant melanoma
Genomic analyses in a rapid autopsy cohort study of patients with melanoma identify the genetic and transcriptomic landscape of melanoma with acquired resistance to MAPK inhibitor and immune checkpoint blockade therapies, providing insights for the potential improvement of therapeutic strategies.
- Sixue Liu
- , Prashanthi Dharanipragada
- & Roger S. Lo
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Research Highlight |
CAR T cells show promise in neuroblastoma
Using CAR T cells to treat solid tumors is notoriously challenging, but a new study shows impressive responses rates in children with high-risk neuroblastoma.
- Karen O’Leary
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Article
| Open AccessMotixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial
The phase 3 GENESIS trial reports the superiority of the novel CXCR4 inhibitor motixafortide with G-CSF in mobilizing hematopoietic progenitor cells for autologous stem cell transplantation in multiple myeloma.
- Zachary D. Crees
- , Michael P. Rettig
- & John F. DiPersio
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Research Briefing |
High-resolution circulating tumor DNA testing predicts survival in metastatic lung cancer clinical trials
Data from circulating tumor DNA (ctDNA) testing were generated for over 1,900 samples across at least 3 time points in a phase 3 clinical trial and used to build a machine learning model to predict patient survival. The model accurately identified patients with a high risk of disease recurrence and could provide a basis for assigning therapies in phase 1/2 clinical trials.
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Research Briefing |
Clinicogenomic landscape of morphological evolution in lung adenocarcinoma
Lung adenocarcinomas (LUADs) encompass a broad spectrum of histological appearances. We use multi-region, prospective and longitudinal sampling from the TRACERx dataset to show the relationship between LUAD morphologies and their underlying evolutionary genomic landscape, as well as clinical risk and the nature of metastatic dissemination.
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Article |
Evolutionary characterization of lung adenocarcinoma morphology in TRACERx
Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.
- Takahiro Karasaki
- , David A. Moore
- & Mariam Jamal-Hanjani
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Article |
Body composition and lung cancer-associated cachexia in TRACERx
Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.
- Othman Al-Sawaf
- , Jakob Weiss
- & Charles Swanton
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Research Briefing |
Using AI to improve the molecular classification of brain tumors
We used deep neural networks trained on optical histology and open-source genomic data to predict the molecular genetics of brain tumors during surgery. Our results represent how AI-based diagnostics can provide a valuable adjunct to wet laboratory methods for molecular testing in patients with cancer.
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Perspective |
Tumor inflammation-associated neurotoxicity
The authors describe a localized toxicity syndrome that is associated with immunotherapy treatment for CNS tumors and propose a new grading scale—with the goal of promoting research and standardizing both reporting and management.
- Jasia Mahdi
- , Jorg Dietrich
- & Michelle Monje
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Article |
Pembrolizumab and cabozantinib in recurrent metastatic head and neck squamous cell carcinoma: a phase 2 trial
In a phase 2 trial of pembrolizumab and cabozantinib in patients with advanced head and neck cancer, a high clinical benefit rate was achieved, which positively correlated with levels of CD8+ T cell infiltration but not tumor mutational burden.
- Nabil F. Saba
- , Conor E. Steuer
- & Christine H. Chung
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Article
| Open AccessLorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results
In children, adolescents and adults with mutated ALK-driven relapsed or refractory neuroblastoma, a third-generation ALK inhibitor with or without chemotherapy was well tolerated, and recommended phase 2 doses were successfully identified in all patient groups.
- Kelly C. Goldsmith
- , Julie R. Park
- & Yael P. Mossé
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Article |
Neoadjuvant enoblituzumab in localized prostate cancer: a single-arm, phase 2 trial
In a single-arm phase 2 study, enoblituzumab (a humanized, Fc-engineered, B7-H3-targeting antibody) was found to be safe and showed preliminary evidence of potential clinical activity in men with high-risk localized prostate cancer.
- Eugene Shenderov
- , Angelo M. De Marzo
- & Emmanuel S. Antonarakis
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Article
| Open AccessConcurrent intrathecal and intravenous nivolumab in leptomeningeal disease: phase 1 trial interim results
In an interim analysis of a phase 1 trial of concurrent intrathecal and intravenous anti-PD1 delivery in patients with leptomeningeal disease and melanoma, treatment was feasible and well-tolerated with no dose-limiting toxicities.
- Isabella C. Glitza Oliva
- , Sherise D. Ferguson
- & Michael A. Davies
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News & Views |
Linking the microbiome to CAR-T cell responses
The composition of the intestinal microbiome may predict clinical outcomes of CAR-T cell therapy for lymphoma, which could inform microbiota-based intervention strategies.
- Zachariah DeFilipp
- & Marcela V. Maus
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Brief Communication |
Artificial-intelligence-based molecular classification of diffuse gliomas using rapid, label-free optical imaging
DeepGlioma, a multimodal deep learning approach for intraoperative diagnostic screening of diffuse glioma, trained on stimulated Raman histology and large-scale public genomic data, can predict molecular alterations for diffuse glioma diagnosis with high accuracy.
- Todd Hollon
- , Cheng Jiang
- & Daniel A. Orringer
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News & Views |
Accurate diagnosis of pediatric brain cancers
Integrative approaches continue to improve diagnostic accuracy for pediatric brain cancers, but much more is needed from researchers, governments and regulators if precision medicine with curative treatments are to become a reality.
- Pratiti Bandopadhayay
- & Elaine R. Mardis
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Article
| Open AccessDiagnostic classification of childhood cancer using multiscale transcriptomics
A new multilevel clustering approach applied retrospectively to 13,000 transcriptomes of different tumors reveals a new diagnostic classification of childhood cancers, in some cases allowing a better prediction of disease outcomes.
- Federico Comitani
- , Joshua O. Nash
- & Adam Shlien
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Research Highlight |
Earlier appears better for immunotherapy in melanoma
For patients with advanced, resectable melanoma, treatment with pembrolizumab before as well as after surgery led to improved outcomes — without additional toxicity.
- Karen O’Leary
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