Inflammation-induced radioresistance is mediated by ROS-dependent inactivation of protein phosphatase 1 in non-small cell lung cancer cells

Abstract Inflammation plays a pivotal role in modulating the radiation responsiveness of tumors. We determined that an inflammation response prior to irradiation contributes to radiotherapy resistance in non-small cell lung cancer (NSCLC) cells. In the clonogenic survival assay, activation of the inflammation response by lipopolysaccharide (LPS) decreased the degree of radiosensitivity in NCI-H460 cells (relatively radiosensitive cells), but had no effect in A549 cells (relatively radioresistant cells). LPS-induced radioresistance of NCI-H460 cells was also confirmed with a xenograft mouse model. The radioresistant effect observed in NCI-H460 cells was correlated with inhibition of apoptotic cell death due to reduced Caspase 3/7 activity. Moreover, we found that the levels of reactive oxygen species (ROS) were synergistically elevated in NCI-H460 cells by treatment with LPS and radiation. Increased ROS generation negatively affected the activity of protein phosphatase 1 (PP1). Decreased PP1 activity did not lead to Bad dephosphorylation, consequently resulting in the inhibition of irradiation-induced mitochondrial membrane potential loss and apoptosis. We confirmed that pre-treatment with a PP1 activator and LPS sensitized NCI-H460 cells to radiation. Taken together, our findings provided evidence that PP1 activity is critical for radiosensitization in NSCLC cells and PP1 activators can serve as promising radiosensitizers to improve therapeutic efficacy.
Source: Apoptosis - Category: Molecular Biology Source Type: research

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ConclusionT-cirDNA could be a novel biomarker representing adaptive immune resistance in NSCLC patients. Further exploration as a predictive biomarker for EGFR inhibitors in setting ofEGFR mutation might be warranted.
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
ConclusionRegardless of the NSCLC patients who were less or more than 65  years, immune checkpoint inhibitors could achieve better OS than chemotherapy. But there was no significant difference when NSCLC patients who were more than 75 years old. Older patient should be offered immune therapies if it is possible and the mechanism in old age treatment should be further s tudied.
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSION: While pembrolizumab is superior to standard chemotherapy in improving overall survival and progression-free survival, results suggest that it is unlikely to be cost-effective at its current price in Singapore. Factors including clinical effectiveness, safety and budget impact should also be considered when making national funding decisions. PMID: 32462958 [PubMed - as supplied by publisher]
Source: Journal of Medical Economics - Category: Health Management Tags: J Med Econ Source Type: research
Adjuvant therapy with osimertinib yielded a nearly 80% reduction in the risk of disease recurrence or death in patients with stage IB-IIIA non – small cell lung cancer with EGFR mutations in the ADAURA   trial.Medscape Medical News
Source: Medscape Hematology-Oncology Headlines - Category: Cancer & Oncology Tags: Hematology-Oncology News Source Type: news
A better understanding of the role of HER2 alterations in non-small cell lung cancer could aid in the development of more targeted therapies.JCO Precision Oncology
Source: Medscape Today Headlines - Category: Consumer Health News Tags: Hematology-Oncology Journal Article Source Type: news
      ·Rozlytrek has shown durable responses across multiple tumour types, including cancer that has spread to the brain, and could become Roche ’s first tumour-agnostic therapy in EuropeBasel, 29 May 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Medicines Agency ’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion under conditional marketing authorisation for Rozlytrek® (entrectinib) for the treatment of adult and paediatric patients 12 years of age and older with solid tumours expressing a neurotrop...
Source: Roche Media News - Category: Pharmaceuticals Source Type: news
Basel, 29 May 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today presented updated data from the pivotal phase III ALEX study, showing an increased five-year survival rate with Alecensa ® (alectinib), compared with crizotinib, in people living with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). These data confirm the longer-term efficacy of Alecensa already demonstrated across three phase III clinical trials. Full findings were presented at the ASCO2 0 Virtual Scientific Programme, on 29 May 2020.“These data further support Alecensa as the standard of care for people with metastatic AL...
Source: Roche Investor Update - Category: Pharmaceuticals Source Type: news
(University of Texas M. D. Anderson Cancer Center) Patients with advanced non-small cell lung cancer (NSCLC) and the MET exon 14 (METex14) skipping mutation had a 46.5% objective response rate to the targeted therapy drug tepotinib, as shown in a study published today in the New England Journal of Medicine and presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting ASCO20 Virtual Meeting (Abstract 9556 - Poster 322) by researchers from The University of Texas MD Anderson Cancer Center.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
ConclusionsLow ‐dose hilar SBRT was efficacious and well‐tolerated, with impressive overall survival and no grade ≥ 3 toxicity. Repeat treatments with SBRT were feasible and effective, demonstrating overall survival, local control, and toxicity comparable to primary treatments.Key pointsSignificant findings of the study Low ‐dose hilar SBRT was efficacious and well‐tolerated Repeated treatments with SBRT demonstrated encouraging results, comparable to primary treatmentsWhat this study adds This study contributes to the small body of literature concerning hilar SBRT Repeat hilar SBRT was safe and fe...
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
In patients with non ‐small cell lung cancer (NSCLC), stereotactic radiotherapy (SRT) is one of the standard therapies for those suffering with intracranial metastatic NSCLC. Radiation‐induced necrosis (RIN) sometimes occurs as the result of the delayed effects of SRT. The magnetic resonance imaging (MRI) of RIN typ ically shows hypointense and hyperintense lesions on T1‐ and T2‐weighted images, respectively. We herein report a patient with a growing brain cystic lesion mimicking RIN adjacent to a post‐radiation brain metastasis from NSCLC harboring anaplastic lymphoma kinase rearrangement. The patient un derwent...
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: CASE REPORT Source Type: research
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