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| Open AccessTrastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial
Exploratory analyses of the DESTINY-Gastric01 trial show that baseline HER2-associated biomarkers in circulating tumor DNA or tissue samples were associated with therapeutic response in patients with HER2-positive tumors, and these analyses identify potential drivers of resistance.
- Kohei Shitara
- , Yung-Jue Bang
- & Kensei Yamaguchi
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Article
| Open AccessPemigatinib in previously treated solid tumors with activating FGFR1–FGFR3 alterations: phase 2 FIGHT-207 basket trial
In a tumor-agnostic phase 2 basket trial, the oral FGFR1–FGFR3 inhibitor pemigatinib elicits responses in tumor types beyond cholangiocarcinoma and bladder cancer and in tumor types with rarer FGFR alterations, with insights provided into resistance mechanisms.
- Jordi Rodón
- , Silvia Damian
- & Lipika Goyal
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Article
| Open AccessMicrobiome confounders and quantitative profiling challenge predicted microbial targets in colorectal cancer development
Controlling for confounders calls into question the robustness of some associations of microbiota with colorectal cancer stages.
- Raúl Y. Tito
- , Sara Verbandt
- & Jeroen Raes
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Article
| Open AccessPersonalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma: a phase 1/2 trial
Treatment of patients with advanced hepatocellular carcinoma with a personalized DNA vaccine in combination with anti-PD-1 therapy was safe and led to encouraging clinical efficacy, with immunological analyses confirming the induction of tumor antigen-specific T cell responses.
- Mark Yarchoan
- , Edward J. Gane
- & Niranjan Y. Sardesai
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Article |
A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results
In an interim analysis of a phase 1/2 trial, a heterologous prime boost vaccine comprised of a chimpanzee adenovirus and self-amplifying mRNA that encodes neoantigens derived from common oncogenic driver mutations in combination with immune checkpoint blockade was safe and elicited neoantigen-specific T cell responses in patients with advanced solid tumors.
- Amy R. Rappaport
- , Chrisann Kyi
- & Karin Jooss
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Article |
Combined anti-PD-1, HDAC inhibitor and anti-VEGF for MSS/pMMR colorectal cancer: a randomized phase 2 trial
In a randomized phase 2 trial comparing anti-PD-1 plus anti-VEGF plus an HDAC inhibitor versus anti-PD-1 plus an HDAC inhibitor in patients with MSS/pMMR colorectal cancer, the triplet combination led to significantly better 18-week progression-free survival.
- Feng Wang
- , Ying Jin
- & Rui-Hua Xu
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Article
| Open AccessRegorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial
In the phase 2 RENOBATE trial, the combination of regorafenib and nivolumab as first-line treatment for unresectable hepatocellular carcinoma exhibited a safe profile and met the primary endpoint with a 31% overall response rate.
- Hyung-Don Kim
- , Seyoung Jung
- & Changhoon Yoo
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Article |
First-line sugemalimab with chemotherapy for advanced esophageal squamous cell carcinoma: a randomized phase 3 study
In a prespecified interim analysis of the phase 3 trial GEMSTONE-304, anti-PD-L1 with chemotherapy versus chemotherapy alone led to significantly prolonged progression-free survival and overall survival of patients with unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.
- Jin Li
- , Zhendong Chen
- & Jason Yang
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Article |
Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma
Cohort-scale integration of clinical and proteomic data from tumor tissues in patients with pancreatic ductal adenocarcinoma led to the identification of a prognostic risk model for patient stratification as well as biomarkers of response to adjuvant chemotherapy, validated in independent external cohorts.
- Lingxi Jiang
- , Jiejie Qin
- & Baiyong Shen
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Article
| Open AccessLymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial
In a phase 1 trial, a lymph node-targeting mutant KRAS peptide vaccine combined with CpG adjuvant is safe, reduces expression of tumor biomarkers and elicits mutant KRAS-specific T cells in patients with pancreatic cancer and colorectal cancer.
- Shubham Pant
- , Zev A. Wainberg
- & Eileen M. O’Reilly
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Article
| Open AccessNeoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial
A neoadjuvant treatment regimen of anti-PD-L1 monotherapy followed by anti-PD-L1 plus chemotherapy was well tolerated and led to a major pathologic response rate of 70% in patients with resectable gastric or gastroesophageal junction adenocarcinoma.
- Yara L. Verschoor
- , Joris van de Haar
- & Myriam Chalabi
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Article |
Sotorasib with panitumumab in chemotherapy-refractory KRASG12C-mutated colorectal cancer: a phase 1b trial
A substudy of the CodeBreaK 101 trial, this phase 1b trial testing the KRAS-G12C inhibitor sotorasib with an anti-EGFR antibody shows an acceptable safety profile of this combination and encouraging preliminary clinical efficacy in patients with chemotherapy-refractory colorectal cancer.
- Yasutoshi Kuboki
- , Marwan Fakih
- & David S. Hong
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Article |
Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial
In the phase 2 trial NEOSUMMIT-01, perioperative treatment of patients with locally advanced gastric or gastro-esophageal junction adenocarcinoma with anti-PD-1 and SOX/XELOX versus SOX/XELOX alone improved pathological complete response or near-complete response rate.
- Shu-Qiang Yuan
- , Run-Cong Nie
- & Feng Wang
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Article
| Open AccessDivarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial
In an arm of a phase 1b trial, the combination of divarasib, a KRAS G12C inhibitor, and cetuximab, an epidermal growth factor receptor inhibitor, was well tolerated with an encouraging overall response rate of 62.5% in patients with KRAS G12C-positive colorectal cancer.
- Jayesh Desai
- , Guzman Alonso
- & Sae-Won Han
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Article
| Open AccessLarge-scale pancreatic cancer detection via non-contrast CT and deep learning
A deep learning model provides high accuracy in detecting pancreatic lesions in multicenter data, outperforming radiology specialists.
- Kai Cao
- , Yingda Xia
- & Jianping Lu
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Article
| Open AccessZolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial
In the randomized, double-blind, phase 3 GLOW trial, capecitabine and oxaliplatin combined with zolbetuximab, a monoclonal antibody that targets CLDN18.2, significantly improved progression-free survival and overall survival in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.
- Manish A. Shah
- , Kohei Shitara
- & Rui-Hua Xu
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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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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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Article
| Open AccessCodon-specific KRAS mutations predict survival benefit of trifluridine/tipiracil in metastatic colorectal cancer
A combination of real-world evidence and a reanalysis of phase 3 clinical trial data unveils KRAS codon G12 mutations as a biomarker of resistance to trifluridine/tipiracil in metastatic colorectal cancer.
- Joris van de Haar
- , Xuhui Ma
- & Nicola Valeri
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Article
| Open AccessFirst-line serplulimab or placebo plus chemotherapy in PD-L1-positive esophageal squamous cell carcinoma: a randomized, double-blind phase 3 trial
The combination of anti-PD-1 treatment with cisplatin and 5-fluorouracil in patients with previously untreated, PD-L1-positive esophageal squamous cell carcinoma improved progression-free survival and overall survival.
- Yan Song
- , Bo Zhang
- & Jing Huang
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News & Views |
Seeking therapeutic synergy in BRAF mutant colorectal cancer
In a phase I trial, the combination of dabrafenib, trametinib and spartalizumab uncovers the crosstalk between the MAPK pathway and the immune system, which offers a promising new strategy to improve clinical outcomes.
- Elena Elez
- , Javier Ros
- & Josep Tabernero
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Article
| Open AccessCombined PD-1, BRAF and MEK inhibition in BRAFV600E colorectal cancer: a phase 2 trial
Patients with BRAFV600E-mutated colorectal cancer have encouraging overall response rates to inhibition of PD-1, BRAF and MEK, with translational analyses suggesting that induction of tumor-intrinsic programs and immune programs contributes to improved outcomes via MAPK inhibition.
- Jun Tian
- , Jonathan H. Chen
- & Ryan B. Corcoran
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Article
| Open AccessMolecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer
In the observational GALAXY arm of the CIRCULATE-Japan study, among 1,049 patients with stage II–IV colorectal cancer, those with presence of circulating tumor DNA (ctDNA) after tumor resection have a high recurrence risk and are likely to benefit from adjuvant chemotherapy.
- Daisuke Kotani
- , Eiji Oki
- & Takayuki Yoshino
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Multistain deep learning for prediction of prognosis and therapy response in colorectal cancer
A deep learning model trained on multiple tumor immune cell stainings from patients with colorectal cancer outperforms currently used clinical and single tumor immune cell staining-based parameters in predicting prognosis. The model can also predict the response to neoadjuvant therapy.
- Sebastian Foersch
- , Christina Glasner
- & Moritz Jesinghaus
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Research Briefing |
A biomarker of response to therapy in metastatic BRAFV600E colorectal cancers
Colorectal cancers expressing the mutant BRAFV600E comprise 10% of all metastatic colorectal cancers, present with a poor prognosis, and are refractory to common therapies. We discovered that a subgroup of these tumors that carries loss-of-function RNF43 mutations is associated with significantly improved response to the current standard-of-care anti-BRAF–anti-EGFR combination therapy.
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Article
| Open AccessRNF43 mutations predict response to anti-BRAF/EGFR combinatory therapies in BRAFV600E metastatic colorectal cancer
The presence of inactivating mutations in RNF43, a negative regulator of WNT, in tumor cells predicts improved response rates and survival outcomes in patients with metastatic BRAFV600E colorectal cancer treated with anti-BRAF/EGFR therapy.
- Elena Elez
- , Javier Ros
- & Rodrigo A. Toledo
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Article |
Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: phase 1 trial interim results
An individualized, heterologous chimpanzee adenovirus (ChAd68) and self-amplifying mRNA-based neoantigen vaccine is safe and well tolerated in patients, warranting further studies to test its potential to rescue response to checkpoint blockade in tumors of low immune reactivity.
- Christine D. Palmer
- , Amy R. Rappaport
- & Karin Jooss
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Article |
Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer
DNA and RNA sequencing in large cohorts of patients with rectal cancer treated with neoadjuvant therapies identifies biomarkers of response that could inform patient selection for non-operative treatment strategies.
- Walid K. Chatila
- , Jin K. Kim
- & Julio Garcia-Aguilar
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Article
| Open AccessCirculating tumor DNA to guide rechallenge with panitumumab in metastatic colorectal cancer: the phase 2 CHRONOS trial
In a phase 2 trial, monitoring tumor resistance mutations in blood using liquid biopsies allowed rationally guided subsequent therapy with anti-EGFR antibodies in patients with colorectal cancer.
- Andrea Sartore-Bianchi
- , Filippo Pietrantonio
- & Alberto Bardelli
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Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma
Multiomics analysis of tumor samples from the phase 1b GO30140 and phase 3 IMbrave150 trials reveals baseline immune and genetic features that might identify patients with advanced hepatocellular carcinoma who will benefit from atezolizumab and bevacizumab combination therapy.
- Andrew X. Zhu
- , Alexander R. Abbas
- & Yulei Wang
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Article
| Open AccessSotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial
In a randomized phase 2 trial, sotigalimab, a CD40 agonist, did not significantly improve overall survival in patients with previously untreated metastatic pancreatic cancer when combined with chemotherapy or with nivolumab and chemotherapy. Multi-omic exploratory analyses provide insights into immunologic features associated with clinical benefit.
- Lacey J. Padrón
- , Deena M. Maurer
- & Robert H. Vonderheide
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Article
| Open AccessClaudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results
In an interim analysis of a phase 1 trial, CAR T cells specific for Claudin18.2, a tight junction protein isoform highly expressed on gastrointestinal tract tumors, were well-tolerated and exhibited promising clinical activity in patients with gastrointestinal cancers.
- Changsong Qi
- , Jifang Gong
- & Lin Shen
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Research Highlight |
A new treatment combination for liver cancer
Gefitinib with lenvatinib shows promising antitumor activity in patients whose cancers had progressed on lenvatinib monotherapy.
- Karen O’Leary
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Brief Communication
| Open AccessCytokine release syndrome in a patient with colorectal cancer after vaccination with BNT162b2
A rare case of cytokine release syndrome in a patient on anti-PD-1 blockade that was likely related to BNT162b2 vaccination supports prospective monitoring of patients with cancer after COVID-19 vaccine administration.
- Lewis Au
- , Annika Fendler
- & Samra Turajlic
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Triage-driven diagnosis of Barrett’s esophagus for early detection of esophageal adenocarcinoma using deep learning
A clinician-in-the-loop deep learning system streamlines the workflow of pathologists for detection of Barrett’s esophagus and retains the diagnostic accuracy of full manual review.
- Marcel Gehrung
- , Mireia Crispin-Ortuzar
- & Florian Markowetz
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Single-cell dissection of intratumoral heterogeneity and lineage diversity in metastatic gastric adenocarcinoma
Single-cell analysis of gastric cancer samples tracks the cell of origin of metastatic lesions and identifies an independent prognostic signature of the clinical outcome.
- Ruiping Wang
- , Minghao Dang
- & Linghua Wang
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Letter |
Colibactin DNA-damage signature indicates mutational impact in colorectal cancer
Identification of a DNA-damage signature induced by colibactin, a toxin expressed by some strains of Escherichia coli, is enriched in human colorectal cancers.
- Paulina J. Dziubańska-Kusibab
- , Hilmar Berger
- & Thomas F. Meyer
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Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer
Local microbiome composition influences treatment efficacy of chemotherapy in colon cancer via modulation of tolerogenic versus immunogenic ileal intestinal epithelial cell death, which in turn influences follicular helper T cell priming.
- Maria Paula Roberti
- , Satoru Yonekura
- & Laurence Zitvogel
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Resource |
A rectal cancer organoid platform to study individual responses to chemoradiation
Rectal cancer organoids retain the pathological features of matched patient tumors and recapitulate clinical responses to chemoradiation.
- Karuna Ganesh
- , Chao Wu
- & J. Joshua Smith
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Letter |
Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer
Colorectal cancer stages are associated with distinct microbial and metabolomic profiles that could shed light on cancer progression.
- Shinichi Yachida
- , Sayaka Mizutani
- & Takuji Yamada
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Brief Communication |
Deep learning can predict microsatellite instability directly from histology in gastrointestinal cancer
A deep residual learning framework identifies microsatellite instability in histology slides from patients with cancer and can be used to guide immunotherapy.
- Jakob Nikolas Kather
- , Alexander T. Pearson
- & Tom Luedde
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Article |
Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer
Blockade of intrahepatic accumulation and function of platelets represents a potential approach to treat non-alcoholic steatohepatitis (NASH) and prevent subsequent progression to hepatocellular carcinoma
- Mohsen Malehmir
- , Dominik Pfister
- & Mathias Heikenwalder
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Article |
Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer
Cross-study analysis defines fecal microbial species associated with colorectal cancer.
- Jakob Wirbel
- , Paul Theodor Pyl
- & Georg Zeller
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Article |
Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation
Multicohort analysis identifies microbial signatures of colorectal cancer in fecal microbiomes.
- Andrew Maltez Thomas
- , Paolo Manghi
- & Nicola Segata
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Letter |
Protective autophagy elicited by RAF→MEK→ERK inhibition suggests a treatment strategy for RAS-driven cancers
Targeted inhibition of RAF–MEK–ERK signaling induces autophagy through the LKB1–AMPK axis, creating a therapeutic vulnerability that can be exploited for treating patients with pancreatic cancer and potentially other RAS-mutant tumors.
- Conan G. Kinsey
- , Soledad A. Camolotto
- & Martin McMahon
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Article |
Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer
Blockade of ERK signaling in KRAS-mutant pancreatic cancer increases the dependence on autophagic flux through different mechanisms and provides a rationale for combinatorial targeting with autophagy inhibitors.
- Kirsten L. Bryant
- , Clint A. Stalnecker
- & Channing J. Der
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Article |
Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer
Microsatellite instability and Epstein–Barr virus positivity represent novel biomarkers of clinical response to PD-1 blockade in patients with metastatic gastric cancer.
- Seung Tae Kim
- , Razvan Cristescu
- & Won Ki Kang
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News & Views |
A treatment strategy for KRAS-driven tumors
Studies in KRAS-mutant lung and pancreatic adenocarcinoma and in KRAS-amplified gastric carcinoma reveal that SHP2 inhibition augments the antitumor effect of MEK inhibitor treatment.
- Trang T. Mai
- & Piro Lito