ArticleThe oncologist2019
Analysis of DNA Damage Response Gene Alterations and Tumor Mutational Burden Across 17,486 Tubular Gastrointestinal Carcinomas: Implications for Therapy.
Article in The oncologist, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04761744 (A Phase II Study of Nivolumab in Patients With Genetic Alterations in DNA Damage Repair and Response Who Progressed After Standard Treatment for Metastatic Solid Cancers), which is not on this map. Cited by 58 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase II Study of Nivolumab in Patients With Genetic Alterations in DNA Damage Repair and Response Who Progressed After Standard Treatment for Metastatic Solid Cancers
Who cites it
58 citing papers in PubMed, 92 citations in OpenAlex.
- Mismatch Repair as a Dynamic and Clinically Actionable Vulnerability in Cancer.Cancer research · 2025Review
- The prognostic and predictive value of homologous recombination deficiency in gastrointestinal cancer.The oncologist · 2025Review
- Targeting Arachidonic Acid Metabolism Enhances Immunotherapy Efficacy in ARID1A-Deficient Colorectal Cancer.Cancer research · 2025Article
- Tumor Mutation Burden Survey of AACR GENIE Database Revealed NTRK (NTRK+) and RET (RET+) Fusions Positive Colorectal Carcinoma (CRC) as Distinct Subsets.Cancer medicine · 2025Article
- Inflammation‑based prognostic markers in patients with advanced or recurrent gastric cancer treated with nivolumab: Tokushukai REAl‑world Data project 02 (TREAD 02).Molecular and clinical oncology · 2024Article
- Construction and validation of a colon cancer prognostic model based on tumor mutation burden-related genes.Scientific reports · 2024Article
- Genomic characterization and immunotherapy for microsatellite instability-high in cholangiocarcinoma.BMC medicine · 2024Article
- Detection of genomic variants in BRCA1 and BRCA2 across gastric cancer patients using next generation sequencing.American journal of translational research · 2024Article
- The co-inhibitory immune checkpoint proteins B7-H1(PD-L1) and B7-H4 in high grade glioma: From bench to bedside.Translational oncology · 2024Article
- Relationship among DDR gene mutations, TMB and PD-L1 in solid tumour genomes identified using clinically actionable biomarker assays.NPJ precision oncology · 2023Article
- Article
- The effects of altered DNA damage repair genes on mutational processes and immune cell infiltration in esophageal squamous cell carcinoma.Cancer medicine · 2023Article
- Article
- Recent advances in immunotherapy and molecular targeted therapy for gastric cancer.Future science OA · 2023Review
- Biomarkers for immunotherapy in esophageal cancer.Frontiers in immunology · 2023Review
- SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance.Cancer research · 2022Article
- The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy.Journal of experimental & clinical cancer research : CR · 2022Review
- Liquid biopsies to monitor and direct cancer treatment in colorectal cancer.British journal of cancer · 2022Review
- The putative oncogenic role of WDTC1 in colorectal cancer.Carcinogenesis · 2022Article
- Genomic Analysis of Waterpipe Smoke-Induced Lung Tumor Autophagy and Plasticity.International journal of molecular sciences · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlterations in the DNA damage response (DDR) pathway confer sensitivity to certain chemotherapies, radiation, and other DNA damage repair targeted therapies. MATERIALS AND
methodsTumor samples from 17,486 unique patients with advanced colorectal, gastroesophageal, or small bowel carcinomas were assayed using hybrid-capture-based comprehensive genomic profiling including sequencing of 10 predefined DDR genes:
resultsDDR alterations were found in 17% of cases: gastric adenocarcinoma 475/1,750 (27%), small bowel adenocarcinoma 148/666 (22%), esophageal adenocarcinoma 467/2,501 (19%), and colorectal cancer 1,824/12,569 (15%).
conclusionThis is the largest study to examine selected DDR defects in tubular GI cancers and confirms that DDR defects are relatively common and that there is an association between the selected DDR defects and a high TMB in more than 20% of cases. Microsatellite stable DDR-defective tumors with elevated TMB warrant further exploration. IMPLICATIONS FOR PRACTICE: Deleterious DNA damage response (DDR) alterations may sensitize tumor cells to poly (ADP-ribose) polymerase inhibition, but also potentially to immune checkpoint inhibitors, owing to accumulation of mutations in DDR-defective tumors. The relevance of DDR defects in gastrointestinal (GI) cancers is understudied. This article characterizes DDR-defective GI malignancies and explores genomic context and tumor mutational burden to provide a platform for future rational investigations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.