دورية أكاديمية
In-depth Clinical and Biological Exploration of DNA Damage Immune Response as a Biomarker for Oxaliplatin Use in Colorectal Cancer.
| العنوان: | In-depth Clinical and Biological Exploration of DNA Damage Immune Response as a Biomarker for Oxaliplatin Use in Colorectal Cancer. |
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| المؤلفون: | Malla SB; Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., Fisher DJ; MRC Clinical Trials Unit, University College London, London, United Kingdom., Domingo E; MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Blake A; MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Hassanieh S; MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Redmond KL; Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., Richman SD; Pathology and data analytics, School of Medicine, University of Leeds, Leeds, United Kingdom., Youdell M; MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Walker SM; Almac Diagnostic Services, Craigavon, United Kingdom., Logan GE; Almac Diagnostic Services, Craigavon, United Kingdom., Chatzipli A; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Cambridge, United Kingdom., Amirkhah R; Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., Humphries MP; Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., Craig SG; Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., McDermott U; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Cambridge, United Kingdom.; AstraZeneca, United Kingdom., Seymour MT; St James's University Hospital, Leeds, United Kingdom., Morton DG; University of Birmingham, Birmingham, United Kingdom., Quirke P; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Cambridge, United Kingdom., West NP; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Cambridge, United Kingdom., Salto-Tellez M; Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., Kennedy RD; Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., Johnston PG; Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., Tomlinson I; University of Edinburgh, Edinburgh, United Kingdom., Koelzer VH; University of Zurich, Zurich, Switzerland., Campo L; MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Kaplan RS; MRC Clinical Trials Unit, University College London, London, United Kingdom., Longley DB; Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., Lawler M; Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., Maughan TS; MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom. tim.maughan@oncology.ox.ac.uk., Brown LC; MRC Clinical Trials Unit, University College London, London, United Kingdom., Dunne PD |
| مؤلفون مشاركون: | S:CORT consortium |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 Jan 01; Vol. 27 (1), pp. 288-300. Date of Electronic Publication: 2020 Oct 07. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Antineoplastic Combined Chemotherapy Protocols/*pharmacology , Biological Assay/*methods , Biomarkers, Tumor/*genetics , Colorectal Neoplasms/*therapy , DNA Damage/*immunology, Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Chemotherapy, Adjuvant/methods ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/immunology ; Colorectal Neoplasms/mortality ; DNA Damage/drug effects ; DNA Mutational Analysis ; Female ; Fluorouracil/pharmacology ; Fluorouracil/therapeutic use ; Gene Expression Profiling ; Humans ; Leucovorin/pharmacology ; Leucovorin/therapeutic use ; Male ; Microsatellite Instability ; Middle Aged ; Mutation ; Neoadjuvant Therapy/methods ; Organoplatinum Compounds/pharmacology ; Organoplatinum Compounds/therapeutic use ; Progression-Free Survival ; Randomized Controlled Trials as Topic |
| مستخلص: | Purpose: The DNA damage immune response (DDIR) assay was developed in breast cancer based on biology associated with deficiencies in homologous recombination and Fanconi anemia pathways. A positive DDIR call identifies patients likely to respond to platinum-based chemotherapies in breast and esophageal cancers. In colorectal cancer, there is currently no biomarker to predict response to oxaliplatin. We tested the ability of the DDIR assay to predict response to oxaliplatin-based chemotherapy in colorectal cancer and characterized the biology in DDIR-positive colorectal cancer. Experimental Design: Samples and clinical data were assessed according to DDIR status from patients who received either 5-fluorouracil (5-FU) or 5FUFA (bolus and infusion 5-FU with folinic acid) plus oxaliplatin (FOLFOX) within the FOCUS trial ( n = 361, stage IV), or neoadjuvant FOLFOX in the FOxTROT trial ( n = 97, stage II/III). Whole transcriptome, mutation, and IHC data of these samples were used to interrogate the biology of DDIR in colorectal cancer. Results: Contrary to our hypothesis, DDIR-negative patients displayed a trend toward improved outcome for oxaliplatin-based chemotherapy compared with DDIR-positive patients. DDIR positivity was associated with microsatellite instability (MSI) and colorectal molecular subtype 1. Refinement of the DDIR signature, based on overlapping IFN-related chemokine signaling associated with DDIR positivity across colorectal cancer and breast cancer cohorts, further confirmed that the DDIR assay did not have predictive value for oxaliplatin-based chemotherapy in colorectal cancer. Conclusions: DDIR positivity does not predict improved response following oxaliplatin treatment in colorectal cancer. However, data presented here suggest the potential of the DDIR assay in identifying immune-rich tumors that may benefit from immune checkpoint blockade, beyond current use of MSI status. (©2020 American Association for Cancer Research.) |
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| معلومات مُعتمدة: | G0701770 United Kingdom MRC_ Medical Research Council; MC_UU_12023/3 United Kingdom MRC_ Medical Research Council; MC_UU_12023/20 United Kingdom MRC_ Medical Research Council; MC_UU_12023/25 United Kingdom MRC_ Medical Research Council; A13721 United Kingdom CRUK_ Cancer Research UK; MC_EX_G0800814 United Kingdom MRC_ Medical Research Council; MC_UU_00004/01 United Kingdom MRC_ Medical Research Council; C212/A13721 United Kingdom CRUK_ Cancer Research UK; MR/M016587/1 United Kingdom MRC_ Medical Research Council |
| المشرفين على المادة: | 0 (Biomarkers, Tumor) 0 (Organoplatinum Compounds) Q573I9DVLP (Leucovorin) U3P01618RT (Fluorouracil) |
| SCR Protocol: | Folfox protocol |
| تواريخ الأحداث: | Date Created: 20201008 Date Completed: 20220110 Latest Revision: 20240612 |
| رمز التحديث: | 20240612 |
| مُعرف محوري في PubMed: | PMC7614625 |
| DOI: | 10.1158/1078-0432.CCR-20-3237 |
| PMID: | 33028592 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-20-3237 |