Article
|
Open Access
Featured
-
-
Article
| Open Access
Regorafenib plus sintilimab as a salvage treatment for microsatellite stable metastatic colorectal cancer: a single-arm, open-label, phase II clinical trial
The combination of targeted therapeutic agents for metastatic colorectal cancer (mCRC) salvage treatment has potential in clinics. Here this group conducts a single-arm, open-label, phase II trial assessing the combination therapy of regorafenib (tyrosine kinase inhibitor) and sintilimab (PD-1 targeting) as a safe and effective salvage-line treatment for mCRC patients who have progressed upon second-line treatment.
- Rui Liu
- , Zhi Ji
- & Jihui Hao
-
Article
| Open Access
Artificial intelligence links CT images to pathologic features and survival outcomes of renal masses
Distinguishing benign renal masses from malignant renal tumours, and further differentiating indolent from aggressive renal cancers, on computed tomography (CT) scans remains challenging. Here, the authors develop deep learning models for distinguishing benign from malignant renal masses, and differentiating indolent from aggressive renal tumours in a large cohort of preoperative CT scans, obtaining high accuracy and a strong association with clinical outcomes.
- Ying Xiong
- , Linpeng Yao
- & Shuo Wang
-
Article
| Open Access
A multistage drug delivery approach for colorectal primary tumors and lymph node metastases
Lymph node (LN) metastases after primary treatment may end up with disease recurrence and poor survival rate. Here this group designs a phospholipase A2 (sPLA2)-responsive nanosystem delivering doxorubicin for in vivo inhibition of both primary colorectal tumor progression and LN metastasis.
- Yihang Yuan
- , Quanjun Lin
- & Chao Fang
-
Article
| Open Access
WNT11 Promotes immune evasion and resistance to Anti-PD-1 therapy in liver metastasis
Activation of the WNT/β-catenin signaling pathway has been associated with immune evasion in several cancer types. Here the authors show that expression of WNT11, a member of the non-canonical WNT signaling pathway, is associated with CD8 + T cell exclusion and resistance to immune checkpoint inhibitors in liver metastasis.
- Weiliang Jiang
- , Bingjie Guan
- & Senlin Zhao
-
Article
| Open Access
D-2-hydroxyglutarate impairs DNA repair through epigenetic reprogramming
The oncometabolite D-2-HG has been implicated in compromising DNA repair pathway. Here the authors show D-2-HG leads to genome-wide DNA hypermethylation and loss of CTCF coverage, which impairs the assembly of the homologous recombination DNA repair machinery and associated topology adjustment.
- Fengchao Lang
- , Karambir Kaur
- & Chunzhang Yang
-
Article
| Open Access
The anti-PD-L1/CTLA-4 bispecific antibody KN046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma: a phase II trial
KN046 is a bispecific antibody targeting PD-L1 and CTLA4. Here the authors report the results of a phase II trial of KN046 combined with lenvatinib in patients with advanced hepatocellular carcinoma.
- Da Xu
- , Hongwei Wang
- & Baocai Xing
-
Article
| Open Access
A quantitative spatial cell-cell colocalizations framework enabling comparisons between in vitro assembloids and pathological specimens
Comparing spatial omics data across samples remains elusive. Here, the authors develop a quantitative spatial framework, termed as colocatome analysis, by combining pairwise cell-cell colocalization, spatial permutation and normalization approaches for comparing features across conditions and studies.
- Gina Bouchard
- , Weiruo Zhang
- & Sylvia K. Plevritis
-
Article
| Open Access
Brd7 loss reawakens dormant metastasis initiating cells in lung by forging an immunosuppressive niche
Metastasis-initiating cells can reawaken from a dormant state that initially allowed them to survive, triggering metastatic outgrowth. Here, authors show that loss of Brd7 promotes an immunosuppressive tumor microenvironment that drives breast cancer metastatic reawakening from dormancy in the lung.
- Jayanta Mondal
- , Junfeng Zhang
- & Filippo G. Giancotti
-
Article
| Open Access
Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics
Medulloblastoma in children is a difficult cancer to treat and the immune response to this tumour is not fully understood. Here the authors characterise and validate T cell epitopes from these cancers using an immunopeptidomics approach, comparing different molecular subtypes.
- Julia Velz
- , Lena K. Freudenmann
- & Marian C. Neidert
-
Article
| Open Access
Plant-nanoparticles enhance anti-PD-L1 efficacy by shaping human commensal microbiota metabolites
The impact of diet on gut microbiota and metabolites in context of cancer immunotherapy remains elusive. Here the authors reveal ginger-derived exosome-like nanoparticle (GELN) aly-miR159a-3p enhances anti-PD-L1 therapy by increasing microbiota-dependent docosahexaenoic acid (DHA) level thus limiting tumor cell PD-L1 expression.
- Yun Teng
- , Chao Luo
- & Huang-Ge Zhang
-
Article
| Open Access
Stimulus-activated ribonuclease targeting chimeras for tumor microenvironment activated cancer therapy
Off-target effects have limited RNA degradation approaches. Here, the authors develop a tumor microenvironment-activated ribonuclease targeting chimera (RiboTAC) demonstrating H2O2 and acid activated degradation of pre-miR-21, which was effective in restoring radiosensitivity in lung cancer.
- Yuqi Zhang
- , Jinfeng Zhu
- & Haibin Shi
-
Article
| Open Access
USP5 stabilizes YTHDF1 to control cancer immune surveillance through mTORC1-mediated phosphorylation
The m6A binding protein YTHDF1 is frequently upregulated in cancer. Here the authors report that USP5 deubiquitinates and stabilizes YTHDF1, associated with cancer growth and immune evasion, and that targeting USP5 potentiates response to anti-PD-L1 in preclinical models.
- Na Shao
- , Lei Xi
- & Chungang Liu
-
Article
| Open Access
Deep learning to decode sites of RNA translation in normal and cancerous tissues
RNA translation is a core cell process that is deregulated in cancer. Here, the authors show that a machine learning approach, RiboTIE, can reconstruct RNA translation in cancer and non-cancer cells. In medulloblastoma, a brain cancer, RiboTIE enables discovery of subtype-specific microproteins.
- Jim Clauwaert
- , Zahra McVey
- & John R. Prensner
-
Article
| Open Access
Proteomic profiling identifies muscle-invasive bladder cancers with distinct biology and responses to platinum-based chemotherapy
The proteomic landscape of muscle-invasive bladder cancer (MIBC) in the context of platinum-based neoadjuvant chemotherapy (NAC) remains to be explored. Here, proteomic analysis of MIBC tumours pre- and matched post-NAC treatment identifies proteomic clusters with distinct biological and clinical features.
- A. Contreras-Sanz
- , G. L. Negri
- & P. C. Black
-
Comment
| Open Access
Unlocking the potential of engineered immune cell therapy for solid tumors
Adoptive cell therapy has emerged as a promising approach for treating advanced solid malignancies. Genetic engineering techniques represent an exciting area of research for the development of cellular products with enhanced cytotoxicity, phenotype, and metabolism.
- Víctor Albarrán-Fernández
- , Laura Angelats
- & Aleix Prat
-
Article
| Open Access
Molecular and pharmacological heterogeneity of ETV6::RUNX1 acute lymphoblastic leukemia
Acute lymphoblastic leukemias (ALL) with an ETV6::RUNX1 fusion comprise the largest subtype of this cancer, and their optimal treatment strategy remains unclear. Here, the authors perform genomic profiling of 194 ETV6::RUNX1-rearranged pediatric ALL cases, finding two molecular subtypes associated with distinct drug sensitivities.
- Zhenhua Li
- , Huanbin Zhao
- & Jun J. Yang
-
Article
| Open Access
Intricacies of human–AI interaction in dynamic decision-making for precision oncology
AI decision support system non-homogenously influences clinical decisions in dynamic treatment regimen, as it depends on several factors including prior knowledge, preference, disease type, treatment modality, and AI’s learned behavior and inherent biases.
- Dipesh Niraula
- , Kyle C. Cuneo
- & Issam El Naqa
-
Matters Arising
| Open Access
Oligoclonality of TRBC1 and TRBC2 in T cell lymphomas as mechanism of primary resistance to TRBC-directed CAR T cell therapies
- Benjamin Thiele
- , Paul Schmidt-Barbo
- & Mascha Binder
-
Article
| Open Access
Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect
Here, in 3 cohorts of allogeneic stem cell transplant recipients, each receiving FMT from 1 of 3 stool donors for graft-versus-host disease prophylaxis, the authors show that microbiota and clinical outcomes are associated with the specific donor used, suggesting a donor effect with implications for FMT donor selection.
- Swetha Reddi
- , Liliia Senyshyn
- & Armin Rashidi
-
Article
| Open Access
Impact of maternal and offspring smoking and breastfeeding on oesophageal cancer in adult offspring
Early life factors like breastfeeding and maternal smoking may influence oesophageal cancer risk in adults. Here, the authors analyse data from the UK biobank and show that breastfeeding is associated with reduced incidence and mortality of oesophageal cancer and reduced adverse effects of smoking in offspring.
- Yixue Wang
- , Hongru Sun
- & Hang Yin
-
Article
| Open Access
Reconstructing skeletal homeostasis through allogeneic hematopoietic stem cell transplantation in myelofibrosis
Allogenic haematopoietic stem cell transplantation (allo-HSCT) can induce bone marrow fibrosis regression in patients with myelofibrosis (MF) however, the effect on the skeleton is unclear. Here, the authors perform in-depth, longitudinal evaluation of skeletal homeostasis following allo-HSCT in patients with MF using high-resolution imaging and bone biopsy analysis.
- Mathias Schäfersküpper
- , Alexander Simon
- & Tim Rolvien
-
Article
| Open Access
Palmitoylation-dependent regulation of GPX4 suppresses ferroptosis
Ferroptosis is crucial in tumor growth, metastasis, and cancer therapy response. Here, the authors reveal that reversible palmitoylation of GPX4 by ZDHHC20 and APT2 regulates ferroptosis sensitivity, offering a potential target for therapeutic intervention.
- Bin Huang
- , Hui Wang
- & Chengqian Yin
-
Article
| Open AccessDiscordance, accuracy and reproducibility study of pathologists’ diagnosis of melanoma and melanocytic tumors
The accuracy of melanoma diagnosis can vary considerably among clinicians, impacting both patient outcomes and the performance of related AI tools. Here, the authors systematically assess interrater variability among expert pathologists reviewing histopathological images and clinical metadata of melanoma-suspicious lesions collected at eight German hospitals.
- Sarah Haggenmüller
- , Christoph Wies
- & Titus J. Brinker
-
Article
| Open Access
RSK1 is an exploitable dependency in myeloproliferative neoplasms and secondary acute myeloid leukemia
Secondary acute myeloid leukemias (sAMLs) evolving from myeloproliferative neoplasms (MPNs) associate with poor prognosis. Here authors identify RSK1 as a vulnerability for MPN and sAML and show the efficacy of a first-in-class RSK inhibitor, PMD-026, against these types of myeloid malignancies.
- Tim Kong
- , Angelo B. A. Laranjeira
- & Stephen T. Oh
-
Article
| Open Access
Lerociclib plus fulvestrant in patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial
CDK4/6 inhibition is often effective for those with breast cancer but success is limited by adverse reactions. Here, the authors report a phase III randomised trial comparing fulvestrant (oestrogen receptor antagonist) with or without lerociclib (CDK4/6 inhibitor) for the treatment of hormone receptor-positive HER2-negative, endocrine-resistant advanced breast cancer.
- Binghe Xu
- , Qingyuan Zhang
- & Tong Li
-
Article
| Open Access
Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival
Glioma is an aggressive brain tumor subtype with few known risk factors. Here, the authors utilise Mendelian Randomisation to investigate correlation of immune cell counts with subtype-specific risk and mortality in glioma patients.
- Linda Kachuri
- , Geno A. Guerra
- & Stephen S. Francis
-
Article
| Open Access
Integration of clinical, pathological, radiological, and transcriptomic data improves prediction for first-line immunotherapy outcome in metastatic non-small cell lung cancer
Overall survival in metastatic non-small cell lung cancer is improved by immunotherapy but individual responses widely vary, and predictive biomarkers are urgently needed. Here authors show that multimodal markers, based on clinical, pathological, radiological, and transcriptomic data are more reliable at patient risk stratification than unimodal markers, considering one type of input data only.
- Nicolas Captier
- , Marvin Lerousseau
- & Emmanuel Barillot
-
Article
| Open Access
Sitravatinib in combination with nivolumab plus ipilimumab in patients with advanced clear cell renal cell carcinoma: a phase 1 trial
In patients with advanced clear cell renal cell carcinoma (ccRCC), sitravatinib (tyrosine kinase inhibitor) has shown efficacy both alone and in combination with nivolumab (anti-PD-1). Here, the authors investigate triplet combination of sitravatinib with nivolumab and ipilimumab (anti-CTLA4) in patients with metastatic ccRCC and longitudinal single-cell transcriptomic analysis.
- Pavlos Msaouel
- , Kai Yu
- & Jianjun Gao
-
Article
| Open Access
Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial
Combination of immune checkpoint inhibitors with chemoradiation is now standard of care for patients with locally advanced cervical cancer (LACC). Here, the authors report the results of a phase I trial of neoadjuvant vs concurrent atezolizumab (anti-PD-L1) with chemoradiation for LACC.
- Jyoti Mayadev
- , Dmitriy Zamarin
- & Russell J. Schilder
-
Article
| Open Access
Impact of population screening for Lynch syndrome insights from the All of Us data
Lynch Syndrome results in a predisposition to cancer, however, it is frequently undiagnosed prior to cancer occurrence. Here, the authors use All of Us data to report that 63.2% of Lynch syndrome carriers remain undetected due to lack of personal or family cancer history.
- Jiheum Park
- , Hemanth Karnati
- & Fay Kastrinos
-
Article
| Open Access
DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer
Hyperactivation of ribosome biogenesis (RiBi) causes excessive ribosome production, contributing to genome instability and cancer progression. The authors investigate the role of RiBPs in breast cancer, highlighting the upregulation of factors like DCAF13, which enhances cell proliferation by regulating Pol I transcription via K63-linked ubiquitination of RPA194.
- Zhi-Zhi Yang
- , Bing Yang
- & Jian-You Liao
-
Article
| Open Access
Multimodal cell-free DNA whole-genome TAPS is sensitive and reveals specific cancer signals
ctDNA is a useful tool for the diagnosis of cancer, however, it is usually focused on targeted deep sequencing. Here, the authors develop a methodology to assess TET-assisted pyridine borane whole-genome sequencing data for cancer detection without a matched biopsy.
- Dimitrios V. Vavoulis
- , Anthony Cutts
- & Anna Schuh
-
Article
| Open Access
MAT2A inhibitor AG-270/S095033 in patients with advanced malignancies: a phase I trial
AG-270 inhibited the activity of MAT2A and reduced plasma concentrations of SAM by up to 70% in patients with advanced solid tumors. Partial responses were observed in two patients and disease stabilization for ≥4 months was seen in five patients.
- Mrinal Gounder
- , Melissa Johnson
- & Josep Tabernero
-
Article
| Open Access
Selectively expressed RNA molecules as a versatile tool for functionalized cell targeting
Targeting of diseased cells is key to the development of next-generation pharmaceuticals, but is often hindered by a lack of specific cell surface markers. Here the authors develop an RNA-based approach, which allows precise control of gene expression, with translation only occurring within preselected cell types of interest.
- Frederik Rastfeld
- , Marco Hoffmann
- & Bernd Hoffmann
-
Article
| Open Access
Intravenous liposomal irinotecan in metastatic triple-negative breast cancer after ≥ 2 prior lines of chemotherapy: a phase Ib study
Cytotoxic chemotherapy remains the standard treatment for triple negative breast cancer (TNBC), an aggressive subtype of breast cancer associated with poor prognosis. Here the authors report the results of a phase 1b trial of the liposomal irinotecan HE072 in patients with metastatic triple-negative breast cancer after ≥ 2 prior lines of chemotherapy.
- Ying Fan
- , Qingyuan Zhang
- & Binghe Xu
-
Article
| Open Access
Maximizing the clinical utility and performance of cytology samples for comprehensive genetic profiling
Tumour profiling with next-generation sequencing is challenging due to the low amounts of diagnostic material in cytology samples that are obtained through non-invasive procedures. Here, the authors report on the optimization of this process across 4,871 cancer cytology samples profiled by MSK-IMPACT, with emphasis on the successful use of supernatant cell-free DNA.
- David Kim
- , Chad M. Vanderbilt
- & Maria E. Arcila
-
Article
| Open Access
Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial
Several cancer types show dysregulated expression of complement factor H (CFH). Here the authors report the results of a phase 1b dose escalation trial of GT103, a first-in-class, fully human, IgG3 monoclonal antibody targeting CFH, in patients with refractory NSCLC.
- Jeffrey M. Clarke
- , George R. Simon
- & Edward F. Patz Jr
-
Article
| Open Access
Enterocyte-like differentiation defines metabolic gene signatures of CMS3 colorectal cancers and provides therapeutic vulnerability
Colorectal cancer (CRC) is stratified into four consensus molecular subtypes (CMS1-4) but their distinct molecular profiles remain to be understood. Here the authors model the CRC subtypes with genetically engineered mouse organoids, identify the metabolic signature of CMS3 is driven by enterocyte-like differentiation and it could be targeted by inhibition of carbamoyl-phosphate synthase 1.
- Arezo Torang
- , Aleksandar B. Kirov
- & Jan Paul Medema
-
Article
| Open Access
Multiparametric MRI along with machine learning predicts prognosis and treatment response in pediatric low-grade glioma
Understanding the molecular and pathological features of paediatric low-grade glioma (pLGG) is crucial to develop targeted therapies. Here, the authors perform a radiogenomic analysis of pLGGs combining treatment-naïve multiparametric MRI and RNA sequencing, enabling prognostication based on immune profiles as well as prediction of treatment response.
- Anahita Fathi Kazerooni
- , Adam Kraya
- & Ali Nabavizadeh
-
Article
| Open Access
The protein circPETH-147aa regulates metabolic reprogramming in hepatocellular carcinoma cells to remodel immunosuppressive microenvironment
Tumor-associated macrophages (TAMs) are associated with poor prognosis and low responses to immunotherapy. Here, authors discover that a circular RNA, circPETH, produced by TAMs generates a metabolic reprogramming in hepatocellular carcinoma that promotes metastasis and impairs the activity of cytotoxic CD8 + T cells.
- Tian Lan
- , Fengwei Gao
- & Hong Wu
-
Article
| Open Access
ATLAS-seq: a microfluidic single-cell TCR screen for antigen-reactive TCRs
Isolation of antigen-reactive T cell receptors (TCRs) to cancer epitopes is important for engineered T cell immunotherapies. Here the authors show an aptamer-based microfluidic single-cell method to isolate antigen-reactive TCRs and show proof of principle isolations for cytomegalovirus and prostate specific antigen.
- Siwei Luo
- , Amber Notaro
- & Lan Lin
-
Article
| Open Access
Targeting chromosomally unstable tumors with a selective KIF18A inhibitor
Chromosomal instability occurs frequently in cancer, making it an attractive therapeutic target. Here, the authors identify KIF18A as a targetable vulnerability of cancer cells with chromosomal instability and target this using VLS-1272, a selective KIF18A inhibitor.
- Aaron F. Phillips
- , Rumin Zhang
- & Christina H. Eng
-
Article
| Open Access
Next generation thiazolyl ketone inhibitors of cytosolic phospholipase A2 α for targeted cancer therapy
Inhibition of group IVA cytosolic phospholipase A2 (cPLA2α) is a potential approach for cancer treatment. Here, the authors report thiazolyl ketone inhibitors of cPLA2α starting from compound GK470 (AVX235), and the discovery of a more potent and selective lead, GK420 (AVX420), with significant chemotherapeutic properties.
- Felicity J. Ashcroft
- , Asimina Bourboula
- & Berit Johansen
-
Article
| Open Access
Integrating genetic subtypes with PET scan monitoring to predict outcome in diffuse large B-cell lymphoma
The prognostic impact of genetic subtypes in diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS) remains unclear. Here, the authors use data from multiple clinical trials to identify DLBCL-NOS genetic subtypes that are associated with patient outcomes, showing their potential value for prognostic stratification, trial design, and PET response monitoring.
- Matías S. Mendeville
- , Jurriaan Janssen
- & Daphne de Jong
-
Article
| Open Access
Inhalable nanovesicles loaded with a STING agonist enhance CAR-T cell activity against solid tumors in the lung
The efficacy of CAR-T cells is hindered by the immunosuppressive microenvironment of solid tumors. Here the authors report the design and characterization of anti-PD-L1-expressing inhalable nanovesicles loaded with the STING agonist cGAMP, showing enhanced CAR-T cell activity in both orthotopic lung cancer and lung metastasis models.
- Tianchuan Zhu
- , Yuchen Xiao
- & Xi Huang
-
Article
| Open Access
Mitochondrial-cytochrome c oxidase II promotes glutaminolysis to sustain tumor cell survival upon glucose deprivation
Metabolic rewiring supports cancer progression and therapy resistance. Here, the authors show that upregulation of the mitochondrial genome-encoded complex IV protein MT-CO2 is induced upon glucose deprivation to promote glutaminolysis through epigeneticmediated mechanisms.
- Yong Yi
- , Guoqiang Wang
- & Zhi-Xiong Jim Xiao
-
Article
| Open Access
Phthalocyanine aggregates as semiconductor-like photocatalysts for hypoxic-tumor photodynamic immunotherapy
The efficiency of photosensitizers-based photodynamic immunotherapy for cancer treatment is conventionally restricted by the hypoxic tumor microenvironment and oxygen dependence. Here, the authors address these issues by developing a design strategy of converting molecular photosensitizers to semiconductor-like photocatalysts.
- Hao Liu
- , Ziqing Li
- & Xingshu Li
-
Article
| Open Access
PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial
The success of CAR T cell therapies against solid tumors remains limited. Here the authors report the results of a phase 1 trial of PSCA-directed autologous CAR-T cells with pharmacological activation by rimiducid in patients with metastatic pancreatic or prostate cancer.
- Mark N. Stein
- , Ecaterina E. Dumbrava
- & Carlos R. Becerra
-
Article
| Open Access
Characterizing mutation-treatment effects using clinico-genomics data of 78,287 patients with 20 types of cancers
Using clinico-genomic data from 78,287 cancer patients, this study identifies genomic alterations linked to survival outcomes, advancing precision oncology by predicting responses to immunotherapy, chemotherapy, and targeted therapies across 20 cancers.
- Ruishan Liu
- , Shemra Rizzo
- & James Zou
BBOX1 restrains TBK1-mTORC1 oncogenic signaling in clear cell renal cell carcinoma