المؤلفون: Yang C; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.; Division of Drug Screening and Biology Evaluation, Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi 117004, China., Ma S; Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China., Zhang J; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.; Division of Drug Screening and Biology Evaluation, Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi 117004, China., Han Y; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.; Division of Drug Screening and Biology Evaluation, Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi 117004, China., Wan L; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.; Division of Drug Screening and Biology Evaluation, Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi 117004, China., Zhou W; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.; Division of Drug Screening and Biology Evaluation, Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi 117004, China., Dong X; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.; Division of Drug Screening and Biology Evaluation, Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi 117004, China., Yang W; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.; Division of Drug Screening and Biology Evaluation, Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi 117004, China., Chen Y; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.; Division of Drug Screening and Biology Evaluation, Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi 117004, China., Gao L; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.; Division of Drug Screening and Biology Evaluation, Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi 117004, China., Cui W; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China., Jia L; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China., Yang J; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China., Wu C; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China., Wang Q; Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China., Wang L; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.; Division of Drug Screening and Biology Evaluation, Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi 117004, China.

المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jun 04; Vol. 121 (23), pp. e2317790121. Date of Electronic Publication: 2024 May 30.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE

مواضيع طبية MeSH: Lung Neoplasms*/genetics , Lung Neoplasms*/metabolism , Lung Neoplasms*/pathology , Lung Neoplasms*/drug therapy , Carcinoma, Non-Small-Cell Lung*/genetics , Carcinoma, Non-Small-Cell Lung*/metabolism , Carcinoma, Non-Small-Cell Lung*/pathology , Carcinoma, Non-Small-Cell Lung*/drug therapy , Erlotinib Hydrochloride*/pharmacology , Cell Transformation, Neoplastic*/genetics, Humans ; Animals ; Mice ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Drug Resistance, Neoplasm/genetics ; Wnt Signaling Pathway/genetics ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Protein Kinase Inhibitors/pharmacology ; Xenograft Model Antitumor Assays ; Small Cell Lung Carcinoma/genetics ; Small Cell Lung Carcinoma/metabolism ; Small Cell Lung Carcinoma/pathology ; Transcription, Genetic ; Histocompatibility Antigens ; Histone-Lysine N-Methyltransferase

مستخلص: The transformation of lung adenocarcinoma to small cell lung cancer (SCLC) is a recognized resistance mechanism and a hindrance to therapies using epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The paucity of pretranslational/posttranslational clinical samples limits the deeper understanding of resistance mechanisms and the exploration of effective therapeutic strategies. Here, we developed preclinical neuroendocrine (NE) transformation models. Next, we identified a transcriptional reprogramming mechanism that drives resistance to erlotinib in NE transformation cell lines and cell-derived xenograft mice. We observed the enhanced expression of genes involved in the EHMT2 and WNT/β-catenin pathways. In addition, we demonstrated that EHMT2 increases methylation of the SFRP1 promoter region to reduce SFRP1 expression, followed by activation of the WNT/β-catenin pathway and TKI-mediated NE transformation. Notably, the similar expression alterations of EHMT2 and SFRP1 were observed in transformed SCLC samples obtained from clinical patients. Importantly, suppression of EHMT2 with selective inhibitors restored the sensitivity of NE transformation cell lines to erlotinib and delayed resistance in cell-derived xenograft mice. We identify a transcriptional reprogramming process in NE transformation and provide a potential therapeutic target for overcoming resistance to erlotinib.
Competing Interests: Competing interests statement:The authors declare no competing interest.

المؤلفون: Tomic K; Department of Oncology, University Clinical Hospital Mostar, Mostar, Bosnia and Herzegovina., Krpina K; Clinic for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, Zagreb, Croatia., Baticic L; Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Rijeka, Croatia., Samarzija M; Clinic for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, Zagreb, Croatia., Vranic S; College of Medicine, QU Health, Qatar University, Doha, Qatar.

المصدر: Journal of drug targeting [J Drug Target] 2024 Jun; Vol. 32 (5), pp. 499-509. Date of Electronic Publication: 2024 Mar 25.

نوع المنشور: Journal Article; Case Reports; Review

بيانات الدورية: Publisher: Informa Healthcare Country of Publication: England NLM ID: 9312476 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1029-2330 (Electronic) Linking ISSN: 10267158 NLM ISO Abbreviation: J Drug Target Subsets: MEDLINE

مواضيع طبية MeSH: Carcinoma, Non-Small-Cell Lung*/genetics , Carcinoma, Non-Small-Cell Lung*/pathology , Carcinoma, Non-Small-Cell Lung*/drug therapy , ErbB Receptors*/genetics , Lung Neoplasms*/genetics , Lung Neoplasms*/pathology , Lung Neoplasms*/drug therapy , Small Cell Lung Carcinoma*/genetics , Small Cell Lung Carcinoma*/pathology, Humans ; Drug Resistance, Neoplasm ; Immunotherapy/methods ; Mutation ; Protein Kinase Inhibitors/therapeutic use ; Protein Kinase Inhibitors/pharmacology

مستخلص: Histologic transformation to small cell lung cancer (tSCLC) is a rare but increasingly recognised mechanism of acquired resistance to tyrosine kinase inhibitors (TKI) in patients with epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC). Beyond its acknowledged role in TKI resistance, histologic transformation to SCLC might be an important, yet under-recognised, mechanism of resistance in NSCLC treated with immunotherapy. Our review identified 32 studies that investigated tSCLC development in patients with EGFR -mutated NSCLC treated with TKI therapy and 16 case reports of patients treated with immunotherapy. It revealed the rarity of tSCLC, with a predominance of EGFR exon 19 mutations and limited therapeutic options and outcomes. Across all analysed studies in EGFR -mutated NSCLC treated with TKI therapy, the median time to tSCLC development was ∼17 months, with a median overall survival of 10 months. Histologic transformation of EGFR -mutated NSCLC to SCLC is a rare, but challenging clinical problem with a poor prognosis. A small number of documented cases of tSCLC after immunotherapy highlight the need for rebiopsies at progression to diagnose this potential resistance mechanism. Further research is needed to better understand the mechanisms underlying this phenomenon and to develop more effective treatment strategies for patients with tSCLC.

المؤلفون: Cooke SA; Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands., Belderbos JSA; Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands. Electronic address: J.belderbos@nki.nl., Reymen B; Department of Radiation Oncology (MAASTRO Clinic), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands., Lambrecht M; Department of Oncology, Experimental Radiation Oncology, KU Leuven - University of Leuven, Leuven, Belgium; Department of Radiotherapy-Oncology, University Hospitals Leuven, Gasthuisberg, Belgium., Fredberg Persson G; Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Faivre-Finn C; Department of Clinical Oncology, University of Manchester, The Christie NHS Foundation Trust, Manchester, UK., Dieleman EMT; Department of Radiation Oncology, Location AMC, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands., van Diessen JNA; Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands., Sonke JJ; Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands., de Ruysscher D; Department of Radiation Oncology (MAASTRO Clinic), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands.

المصدر: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology [Radiother Oncol] 2024 Jul; Vol. 196, pp. 110312. Date of Electronic Publication: 2024 Apr 24.

نوع المنشور: Journal Article; Randomized Controlled Trial; Clinical Trial, Phase II; Multicenter Study

بيانات الدورية: Publisher: Elsevier Scientific Publishers Country of Publication: Ireland NLM ID: 8407192 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0887 (Electronic) Linking ISSN: 01678140 NLM ISO Abbreviation: Radiother Oncol Subsets: MEDLINE

مواضيع طبية MeSH: Carcinoma, Non-Small-Cell Lung*/radiotherapy , Carcinoma, Non-Small-Cell Lung*/pathology , Lung Neoplasms*/radiotherapy , Lung Neoplasms*/pathology , Patient Reported Outcome Measures* , Quality of Life*, Humans ; Male ; Female ; Middle Aged ; Aged ; Neoplasm Staging ; Radiotherapy Dosage ; Chemoradiotherapy/adverse effects ; Positron-Emission Tomography

مستخلص: Background and Purpose: The ultimate challenge in dose-escalation trials lies in finding the balance between benefit and toxicity. We examined patient-reported outcomes (PROs), including health-related quality of life (HRQoL) in patients with locally advanced non-small cell lung cancer (LA-NSCLC), treated with dose-escalated radiotherapy.
Materials and Methods: The international, randomised, phase 2 ARTFORCE PET-Boost study (NCT01024829) aimed to improve 1-year freedom from local failure rates in patients with stage II-III NSCLC, with a ≥ 4 cm primary tumour. Treatment consisted of an individualised, escalated fraction dose, either to the primary tumour as a whole or to its most FDG-avid subvolume (24 x 3.0-5.4 Gy). Patients received sequential or concurrent chemoradiotherapy, or radiotherapy only. Patients were asked to complete the EORTC QLQ-C30, QLQ-LC13, and the EuroQol-5D at eight timepoints. We assessed the effect of dose-escalation on C30 sum score through mixed-modelling and evaluated clinically meaningful changes for all outcomes.
Results: Between Apr-2010 and Sep-2017, 107 patients were randomised; 102 were included in the current analysis. Compliance rates: baseline 86.3%, 3-months 85.3%, 12-months 80.3%; lowest during radiation treatment 35.0%. A linear mixed-effect (LME) model revealed no significant change in overall HRQoL over time, and no significant difference between the two treatment groups. Physical functioning showed a gradual decline in both groups during treatment and at 18-months follow-up, while clinically meaningful worsening of dyspnoea was seen mainly at 3- and 6-months.
Conclusion: In patients with LA-NSCLC treated with two dose-escalation strategies, the average patient-reported HRQoL remained stable in both groups, despite frequent patient-reported symptoms, including dyspnoea, dysphagia, and fatigue.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)

المؤلفون: Asano Y; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8641, Japan., Hayashi K; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8641, Japan. Electronic address: hysk@med.kanazawa-u.ac.jp., Takeuchi A; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8641, Japan., Kato S; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8641, Japan., Miwa S; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8641, Japan., Taniguchi Y; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8641, Japan., Okuda M; Department of Radiology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8640, Japan., Matsumoto I; Department of Thoracic Surgery, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, 920-8640, Japan., Yano S; Department of Respiratory Medicine, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, 920-8641, Japan., Demura S; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.

المصدر: International immunopharmacology [Int Immunopharmacol] 2024 Jul 30; Vol. 136, pp. 112276. Date of Electronic Publication: 2024 May 30.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE

مواضيع طبية MeSH: Carcinoma, Non-Small-Cell Lung*/drug therapy , Carcinoma, Non-Small-Cell Lung*/blood , Carcinoma, Non-Small-Cell Lung*/immunology , Carcinoma, Non-Small-Cell Lung*/mortality , Lung Neoplasms*/drug therapy , Lung Neoplasms*/blood , Immune Checkpoint Inhibitors*/therapeutic use , Bone Neoplasms*/secondary , Bone Neoplasms*/drug therapy , Bone Neoplasms*/blood , Biomarkers, Tumor*/blood , C-Reactive Protein*/analysis , Neutrophils*/immunology, Humans ; Female ; Male ; Middle Aged ; Aged ; Prognosis ; Inflammation/blood ; Nutrition Assessment ; Aged, 80 and over ; Adult ; Retrospective Studies

مستخلص: Objectives: We aimed to investigate the association of the dynamics of serum inflammatory and nutritional indicators with immune checkpoint inhibitor (ICI) response in non-small-cell lung cancer (NSCLC) with bone metastases, and to develop a novel predictive scoring system based on these indicators.
Methods: Patients with NSCLC having bone metastases treated with ICIs were categorized as: the development cohort (January 2016 to March 2021, n = 60) and the validation cohort (April 2021 to June 2023, n = 40). Serum indicators of inflammation and nutrition such as C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), albumin, prognostic nutritional index (PNI) were investigated before and six weeks after ICI initiation. The correlations of these dynamics with bone metastasis response rate (BoMRR) and overall survival (OS) were analyzed. A scoring system consisting of independent predictors was developed (IMMUNO-SCORE) and correlations with clinical outcomes were validated using the validation cohort.
Results: In the development cohort, multivariable analysis showed that NLR and PNI dynamics and CRP, NLR, and PNI dynamics were independent predictors of BoMRR and OS, respectively. The IMMUNO-SCORE consisting of NLR and PNI dynamics, which were the common predictors of the clinical outcomes, was significantly correlated with BoMRR (p < 0.01) and OS (p < 0.001) in cross-validation. The area under the curve of the score (0.786) was higher than individual NLR and PNI dynamics (0.72 and 0.684).
Conclusion: Dynamics in NLR and PNI were demonstrated as biomarkers of treatment response and prognosis in ICI treatment of NSCLC with bone metastases, and the score combining these biomarkers was significantly correlated with clinical outcomes.
(Copyright © 2024 Elsevier B.V. All rights reserved.)

المؤلفون: Zhang L; Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China., Xu Y; Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China., Cheng Z; Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China., Zhao J; Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China; Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, China., Wang M; Department of Public Laboratory, Tianjin Medical University Cancer Institute & Hospital, 300060, Tianjin, China., Sun Y; Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China., Mi Z; Department of Public Laboratory, Tianjin Medical University Cancer Institute & Hospital, 300060, Tianjin, China; Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, China. Electronic address: mizeyun@tmu.edu.cn., Yuan Z; Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China. Electronic address: zyuan@tmu.edu.cn., Wu Z; Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China; Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, China. Electronic address: zwu08@tmu.edu.cn.

المصدر: Cancer letters [Cancer Lett] 2024 Jul 28; Vol. 595, pp. 217000. Date of Electronic Publication: 2024 May 29.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Elsevier Science Ireland Country of Publication: Ireland NLM ID: 7600053 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7980 (Electronic) Linking ISSN: 03043835 NLM ISO Abbreviation: Cancer Lett Subsets: MEDLINE

مواضيع طبية MeSH: MicroRNAs*/genetics , MicroRNAs*/metabolism , Carcinoma, Non-Small-Cell Lung*/genetics , Carcinoma, Non-Small-Cell Lung*/radiotherapy , Carcinoma, Non-Small-Cell Lung*/pathology , Carcinoma, Non-Small-Cell Lung*/metabolism , Ferroptosis*/genetics , NF-E2-Related Factor 2*/genetics , NF-E2-Related Factor 2*/metabolism , Lung Neoplasms*/genetics , Lung Neoplasms*/pathology , Lung Neoplasms*/radiotherapy , Lung Neoplasms*/metabolism , Radiation Tolerance*/genetics , Early Growth Response Protein 1*/genetics , Early Growth Response Protein 1*/metabolism , Signal Transduction* , Gene Expression Regulation, Neoplastic*, Humans ; Animals ; Cell Line, Tumor ; Mice ; Male ; Reactive Oxygen Species/metabolism ; A549 Cells ; Mice, Nude ; Female

مستخلص: Radiotherapy is one of the predominant treatment modalities for almost all kinds of malignant cancers, including non-small cell lung cancer (NSCLC). Increasing evidence shows that ionizing radiation (IR) induces reactive oxygen species (ROS) leading to lipid peroxidation and subsequently ferroptosis of cancer cells. However, cancer cells evolve multiple mechanisms against ROS biology resulting in resistance to ferroptosis and radiotherapy, of which NRF2 signaling is one of the most studied. In the current research, we identified that microRNA-139 (miR-139) could be a novel radiosensitizer for NSCLC by inhibiting NRF2 signaling. We found that miR-139 possessed great potential as a diagnostic biomarker for NSCLC and multiple other types of cancer. Overexpression of miR-139 increased radiosensitivity of NSCLC cells in vitro and in vivo. MiR-139 directly targeted cJUN and KPNA2 to impair NRF2 signaling resulting in enhanced IR-induced lipid peroxidation and cellular ferroptosis. We proved KPNA2 to be a binding partner of NRF2 that involved in nuclear translocation of NRF2. Moreover, we found that IR induced miR-139 expression through transcriptional factor EGR1. EGR1 bound to the promoter region and transactivated miR-139. Overall, our findings elucidated the effect of EGR1/miR-139/NRF2 in IR-induced ferroptosis of NSCLC cells and provided theoretical support for the potential diagnostic biomarkers and therapeutic targets for the disease.
Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests.
(Copyright © 2024 Elsevier B.V. All rights reserved.)

المؤلفون: Bossé Y; Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada; Department of Molecular Medicine, Université Laval, Quebec City, Canada. Electronic address: yohan.bosse@criucpq.ulaval.ca., Dasgupta A; Oncology Data Science, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA., Abadier M; Translational Medicine Early Oncology, AstraZeneca, Waltham, MA, USA., Guthrie V; Oncology Data Science, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA., Song F; Translational Medicine Early Oncology, AstraZeneca, Munich, Germany., Saavedra Armero V; Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada., Gaudreault N; Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada., Orain M; Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada., Lamaze FC; Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada., Melton C; GRAIL, LLC, Menlo Park, CA, USA., Nance T; GRAIL, LLC, Menlo Park, CA, USA., Hung T; GRAIL, LLC, Menlo Park, CA, USA., Hodgson D; Translational Medicine Early Oncology, AstraZeneca, Cambridge, United Kingdom., Abbosh C; Translational Medicine Early Oncology, AstraZeneca, Cambridge, United Kingdom., Joubert P; Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada; Department of Molecular Biology, Pathology and Medical Biochemistry, Université Laval, Quebec City, Canada.

المصدر: Cancer letters [Cancer Lett] 2024 Jul 10; Vol. 594, pp. 216984. Date of Electronic Publication: 2024 May 24.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Elsevier Science Ireland Country of Publication: Ireland NLM ID: 7600053 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7980 (Electronic) Linking ISSN: 03043835 NLM ISO Abbreviation: Cancer Lett Subsets: MEDLINE

مواضيع طبية MeSH: Carcinoma, Non-Small-Cell Lung*/genetics , Carcinoma, Non-Small-Cell Lung*/surgery , Carcinoma, Non-Small-Cell Lung*/blood , Carcinoma, Non-Small-Cell Lung*/pathology , Circulating Tumor DNA*/blood , Circulating Tumor DNA*/genetics , Lung Neoplasms*/surgery , Lung Neoplasms*/genetics , Lung Neoplasms*/blood , Lung Neoplasms*/pathology , DNA Methylation* , Neoplasm Staging*, Humans ; Male ; Female ; Aged ; Middle Aged ; Retrospective Studies ; Prognosis ; Neoplasm Recurrence, Local/blood ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/pathology ; Biomarkers, Tumor/blood ; Biomarkers, Tumor/genetics

مستخلص: Background: Circulating tumor DNA (ctDNA) positivity at diagnosis, which is associated with worse outcomes in multiple solid tumors including stage I-III non-small cell lung cancer (NSCLC), may have utility to guide (neo)adjuvant therapy.
Methods: In this retrospective study, 260 patients with clinical stage I NSCLC (180 adenocarcinoma, 80 squamous cell carcinoma) were allocated (2:1) to high- and low-risk groups based on relapse versus disease-free status ≤5 years post-surgery. We evaluated the association of preoperative ctDNA detection by a plasma-only targeted methylation-based multi-cancer early detection (MCED) test with NSCLC relapse ≤5 years post-surgery in the overall population, followed by histology-specific subgroup analyses.
Results: Across clinical stage I patients, preoperative ctDNA detection did not associate with relapse within 5 years post-surgery. Sub-analyses confined to lung adenocarcinoma suggested a histology-specific association between ctDNA detection and outcome. In this group, ctDNA positivity tended to associate with relapse within 2 years, suggesting prognostic implications of MCED test positivity may be histology- and time-dependent in stage I NSCLC. Preoperative ctDNA detection was associated with upstaging of clinical stage I to pathological stage II-III NSCLC.
Conclusions: Our findings suggest preoperative ctDNA detection in patients with resectable clinical stage I NSCLC using MCED, a pan-cancer screening test developed for use in an asymptomatic population, has no detectable prognostic value for relapse ≤5 years post-surgery. MCED detection may be associated with early adenocarcinoma relapse and increased pathological upstaging rates in stage I NSCLC. However, given the exploratory nature of these findings, independent validation is required.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Y. Bossé has received grants (paid to institution) from AstraZeneca and the IUCPQ foundation. A. Dasgupta is a full-time employee of and owns stock in AstraZeneca. M. Abadier is a full-time employee of and owns stock in Moderna Therapeutics. V. Guthrie is a full-time employee of and owns stock in Exact Sciences. F. Song is a full-time employee of and owns stock in AstraZeneca. F.C. Lamaze has a patent pending related to cancer diagnosis (U.S. Application No. 17/612,695; filed November 19, 2021). C. Melton is a full-time employee of GRAIL, LLC and owns stock in Illumina, Inc. T. Nance is a full-time employee of GRAIL, LLC. T. Hung is a full-time employee of GRAIL, LLC and owns stock in Illumina, Inc. D. Hodgson is a full-time employee of and owns stock in AstraZeneca. C. Abbosh is a full-time employee of and owns stock in AstraZeneca, and holds patents in MRD detection (ES2913468T3 and US20200248266A1). P. Joubert has received honoraria and research grants from AstraZeneca. The remaining authors declare no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

المؤلفون: Xu M; The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310000, China.; Department of Clinical Trial, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, China., Shao K; Department of Clinical Trial, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, China.; Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310018, Zhejiang, China., Wang Y; The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310000, China.; Department of Clinical Trial, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, China., Hao Y; The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310000, China. deartreasurealicia@163.com.; Department of Clinical Trial, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, China. deartreasurealicia@163.com., Song Z; Department of Clinical Trial, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, China. songzb@zjcc.org.cn.; Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310018, Zhejiang, China. songzb@zjcc.org.cn.

المصدر: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico [Clin Transl Oncol] 2024 Jul; Vol. 26 (7), pp. 1687-1695. Date of Electronic Publication: 2024 Feb 16.

نوع المنشور: Journal Article; Comparative Study

بيانات الدورية: Publisher: Country of Publication: Italy NLM ID: 101247119 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1699-3055 (Electronic) Linking ISSN: 1699048X NLM ISO Abbreviation: Clin Transl Oncol Subsets: MEDLINE

مواضيع طبية MeSH: Indoles*/therapeutic use , Indoles*/administration & dosage , Indoles*/adverse effects , Quinolines*/therapeutic use , Quinolines*/adverse effects , Quinolines*/administration & dosage , Small Cell Lung Carcinoma*/drug therapy , Small Cell Lung Carcinoma*/pathology , Immune Checkpoint Inhibitors*/therapeutic use , Immune Checkpoint Inhibitors*/adverse effects , Immune Checkpoint Inhibitors*/administration & dosage , Brain Neoplasms*/secondary , Brain Neoplasms*/drug therapy , Lung Neoplasms*/drug therapy , Lung Neoplasms*/pathology , Antineoplastic Combined Chemotherapy Protocols*/therapeutic use , Antineoplastic Combined Chemotherapy Protocols*/adverse effects, Humans ; Male ; Female ; Middle Aged ; Aged ; Progression-Free Survival ; Retrospective Studies ; Adult ; Aged, 80 and over ; Kaplan-Meier Estimate

مستخلص: Background: Anlotinib, as a salvage treatment for patients after failure of third-line or later-line treatments for small cell lung cancer (SCLC), has shown efficacy in patients with brain metastases (BMs). However, the efficacy and safety of anlotinib alone or in combination with immunotherapy for SCLC with BMs remain unclear.
Method: Patients treated with anlotinib alone or in combination with an immune checkpoint inhibitor (ICI) at the Zhejiang Cancer Hospital between April 2019 and February 2023 were identified. Kaplan-Meier curves were used to describe the progression-free survival (PFS) and intracranial PFS (iPFS). A waterfall diagram was used to indicate changes in intracranial lesions.
Results: A total of 48 patients were included; 29 received anlotinib alone, and 19 were administered anlotinib plus ICI. Combination therapy, compared with anlotinib, was associated with significantly longer PFS and iPFS (PFS: 8.1 months vs. 2.5 months, P < 0.001; iPFS: 8.1 months vs. 2.5 months, P = 0.004). Similar results were observed in patients with multiple BMs (PFS: 8.1 months vs. 1.9 months, P = 0.001; iPFS: 8.1 months vs. 1.9 months, P = 0.002). After third-line or later-line treatments, patients treated with ICI plus anlotinib also achieved significant PFS and iPFS benefits (PFS: 8.4 months vs. 2.1 months, P < 0.001; iPFS: 9.2 months vs. 2.1 months, P = 0.002). No new or severe adverse events were observed with combination therapy.
Conclusion: The combination of anlotinib and ICI has promising intracranial and extracranial efficacy with tolerable toxicity, and may be a therapeutic option for SCLC patients with BMs.
(© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

المؤلفون: Zhang J; Department of Medical Nutrition, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing 211200, China., Tang X; Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, China., Zhang W; Department of General Surgery, The Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, China., Xu Y; Department of Laboratory Center, The Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, China., Zhang H; Department of General Surgery, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing 211200, China. Electronic address: zhanghengzhj@163.com., Fan Y; Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, China. Electronic address: jszjfanyu@163.com.

المصدر: Clinical nutrition (Edinburgh, Scotland) [Clin Nutr] 2024 Jul; Vol. 43 (7), pp. 1618-1625. Date of Electronic Publication: 2024 May 18.

نوع المنشور: Journal Article; Meta-Analysis; Systematic Review

بيانات الدورية: Publisher: Elsevier Country of Publication: England NLM ID: 8309603 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1983 (Electronic) Linking ISSN: 02615614 NLM ISO Abbreviation: Clin Nutr Subsets: MEDLINE

مواضيع طبية MeSH: Cachexia*/etiology , Cachexia*/mortality , Carcinoma, Non-Small-Cell Lung*/complications , Carcinoma, Non-Small-Cell Lung*/mortality , Lung Neoplasms*/complications , Lung Neoplasms*/mortality, Humans ; Prognosis ; Male ; Female ; Aged ; Middle Aged

مستخلص: Introduction: Cancer cachexia is a complex problem characterized by weight loss due to skeletal muscle and adipose tissue reduction. The purpose of this meta-analysis is to examine the association between cancer cachexia and adverse outcomes in patients with non-small cell lung cancer (NSCLC).
Methods: A comprehensive search was conducted in the PubMed, Web of Science, and Embase databases from their inception to January 15, 2024. Retrospective or prospective studies that investigated the cancer cachexia as a predictor of overall survival (OS), progression-free survival (PFS), overall response rate (ORR), or disease control rate (DCR) in NSCLC patients were included in this analysis.
Results: Sixteen studies, comprising 5919 NSCLC patients, were identified. The pooled prevalence of cachexia in NSCLC patients was 39%, with individual studies reporting rates ranging from 19% to 63.8%. A meta-analysis using a random effects model showed that cachexia was associated with reduced OS (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.54-2.21) and PFS (HR 1.49; 95% CI 1.27-1.73). Subgroup analysis indicated that cancer cachexia significantly predicted OS, regardless of study design, NSCLC subtypes, cancer stage, definitions of cachexia, or follow-up duration. However, there was no clear association between cancer cachexia and ORR or DCR.
Conclusions: Cancer cachexia emerges is a negative prognostic factor for OS and PFS in NSCLC patients. Assessing cancer cachexia can improve risk classification for survival outcomes in this patient population.
Competing Interests: Conflict of interest The authors report no conflict of interest.
(Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

المؤلفون: Chen X; Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China., Yuan M; Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China., Zhong T; Clinical College of Medicine, Jining Medical University, Jining, Shandong, China., Wang M; Department of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China., Wu F; Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China., Lu J; Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China., Sun D; Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China., Xiao C; Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China., Sun Y; Department of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China., Hu Y; Department of Radiation Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX, USA., Wu M; Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China., Wang L; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address: wanglinlinatjn@163.com., Yu J; Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China; Research Unit of Radiation Oncology, Chinese Academy of Medical Sciences, Jinan, Shandong, China. Electronic address: sdyujinming@126.com., Chen D; Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China; Department of Radiation Oncology, Shandong University Cancer Center, Jinan, Shandong, China. Electronic address: dave0505@yeah.net.

المصدر: Cancer letters [Cancer Lett] 2024 Jul 01; Vol. 593, pp. 216930. Date of Electronic Publication: 2024 May 03.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Elsevier Science Ireland Country of Publication: Ireland NLM ID: 7600053 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7980 (Electronic) Linking ISSN: 03043835 NLM ISO Abbreviation: Cancer Lett Subsets: MEDLINE

مواضيع طبية MeSH: Carcinoma, Non-Small-Cell Lung*/radiotherapy , Carcinoma, Non-Small-Cell Lung*/genetics , Carcinoma, Non-Small-Cell Lung*/pathology , Carcinoma, Non-Small-Cell Lung*/metabolism , Cellular Senescence*/radiation effects , Radiation Tolerance*/genetics , Lung Neoplasms*/radiotherapy , Lung Neoplasms*/genetics , Lung Neoplasms*/pathology , Lung Neoplasms*/metabolism , Receptors, Immunologic*/genetics , Receptors, Immunologic*/metabolism, Humans ; Cell Line, Tumor ; Cell Proliferation/radiation effects ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; STAT3 Transcription Factor/metabolism ; STAT3 Transcription Factor/genetics ; Animals ; Janus Kinase 2/metabolism ; Janus Kinase 2/genetics ; Mice ; Signal Transduction ; Gene Expression Regulation, Neoplastic/radiation effects ; Senescence-Associated Secretory Phenotype/genetics ; A549 Cells ; Female

مستخلص: Radiotherapy (RT) in non-small cell lung cancer (NSCLC) triggers cellular senescence, complicating tumor microenvironments and affecting treatment outcomes. This study examines the role of lymphocyte immunoglobulin-like receptor B2 (LILRB2) in modulating RT-induced senescence and radiosensitivity in NSCLC. Through methodologies including irradiation, lentivirus transfection, and various molecular assays, we assessed LILRB2's expression and its impact on cellular senescence levels and tumor cell behaviors. Our findings reveal that RT upregulates LILRB2, facilitating senescence and a senescence-associated secretory phenotype (SASP), which in turn enhances tumor proliferation and resistance to radiation. Importantly, LILRB2 silencing attenuates these effects by inhibiting the JAK2/STAT3 pathway, significantly increasing radiosensitivity in NSCLC models. Clinical data correlate high LILRB2 expression with reduced RT response and poorer prognosis, suggesting LILRB2's pivotal role in RT-induced senescence and its potential as a therapeutic target to improve NSCLC radiosensitivity.
Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

المؤلفون: Wu J; Department of Pathology, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), No. 52, Fu-Cheng Road, Beijing, 100142, China., Sun W; Department of Pathology, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), No. 52, Fu-Cheng Road, Beijing, 100142, China., Zhang Y; Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center of Cancer, Tianjin, China., Mao L; Department of Pathology, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), No. 52, Fu-Cheng Road, Beijing, 100142, China., Ding T; Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center of Cancer, Tianjin, China., Huang X; Department of Pathology, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), No. 52, Fu-Cheng Road, Beijing, 100142, China., Lin D; Department of Pathology, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), No. 52, Fu-Cheng Road, Beijing, 100142, China. lindm3@163.com.

المصدر: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico [Clin Transl Oncol] 2024 Jul; Vol. 26 (7), pp. 1738-1747. Date of Electronic Publication: 2024 Feb 29.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Country of Publication: Italy NLM ID: 101247119 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1699-3055 (Electronic) Linking ISSN: 1699048X NLM ISO Abbreviation: Clin Transl Oncol Subsets: MEDLINE

مواضيع طبية MeSH: Carcinoma, Non-Small-Cell Lung*/drug therapy , Carcinoma, Non-Small-Cell Lung*/genetics , Carcinoma, Non-Small-Cell Lung*/pathology , Carcinoma, Non-Small-Cell Lung*/immunology , Carcinoma, Non-Small-Cell Lung*/surgery , Tumor Microenvironment*/immunology , Lung Neoplasms*/drug therapy , Lung Neoplasms*/genetics , Lung Neoplasms*/immunology , Lung Neoplasms*/pathology , Neoplasm Recurrence, Local*/genetics , Mutation*, Humans ; Female ; Male ; Middle Aged ; Aged ; B7-H1 Antigen ; Chemotherapy, Adjuvant ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Adult ; Biomarkers, Tumor/genetics

مستخلص: Purpose: To investigate the impact of platinum-based adjuvant chemotherapy on the immunotherapeutic biomarkers of postoperative recurrent tumors in non-small cell lung cancer (NSCLC).
Methods: This study involved twenty-two cases of NSCLC, all of which underwent postoperative platinum-based chemotherapy, with matched surgical samples obtained from both their primary tumors (PTs) and recurrent tumors (RTs). Multiplex immunofluorescence was performed to assess the tumor proportion score (TPS) and immune cells (IC) on whole sections. Whole exon sequencing (WES) was conducted to investigate the tumor mutational burden (TMB) and tumor neoantigen burden (TNB).
Results: Compared to paired PTs, RTs exhibited higher PD-L1 expression, along with a slightly elevated density of intratumoral PD-L1+ cells (p = 0.082) and an increased tumor proportion score (mean TPS: 40.51% vs. 28.56%, p = 0.046). Regarding IC infiltration, RTs generally demonstrated significantly lower CD8+  cytotoxic T lymphocyte (CTL) density (p = 0.011) and lower CD68+  macrophage density (p = 0.005), with a loss of tertiary lymphoid structure (TLS). The comparison between RTs and PTs revealed no significant differences in TMB (p = 0.795), whereas the count of TNB in RTs was notably increased compared to PTs (p = 0.033). Prognosis analysis indicated that a higher density of CD8+  CTLs in RTs was positively correlated with improved overall survival (OS).
Conclusions: In NSCLC patients with a history of postoperative platinum-based chemotherapy, the RTs demonstrated a trend towards increased PD-L1 expression and TMB/TNB, but a state of immunosuppression characterized by decreased ICs and loss of TLS, which may potentially impact the therapeutic benefits of immunotherapy.
(© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)