scholarly journals ROS-1 NSCLC therapy resistance mechanism

2021 ◽  
Vol 4 ◽  
pp. 16-16
Author(s):  
Miguel García-Pardo ◽  
Antonio Calles
Keyword(s):  
Resistance Mechanism ◽  
Therapy Resistance

scholarly journals DNA Methylation Analysis in Plasma Cell-Free DNA and Paired CTCs of NSCLC Patients before and after Osimertinib Treatment

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5974
Author(s):  
Aliki Ntzifa ◽  
Dora Londra ◽  
Theodoros Rampias ◽  
Athanasios Kotsakis ◽  
Vassilis Georgoulias ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Resistance Mechanism ◽  
Therapy Resistance ◽  
Methylation Analysis ◽  
Before And After ◽  
Progression Of Disease ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
First Time ◽  
Dna Methylation Analysis

Osimertinib has been an effective second-line treatment in EGFR mutant NSCLC patients; however, resistance inevitably occurs. DNA methylation has been previously implicated in NSCLC progression and often in therapy resistance, however its distinct role in osimertinib resistance is not elucidated as yet. In the present study, we directly compared DNA methylation of nine selected genes (RASSF1A, RASSF10, APC, WIF-1, BRMS1, SLFN11, RARβ, SHISA3, and FOXA1) in plasma-cfDNA and paired CTCs of NSCLC patients who were longitudinally monitored during osimertinib treatment. Peripheral blood (PB) from 42 NSCLC patients was obtained at two time points: (a) baseline: before treatment with osimertinib and (b) at progression of disease (PD). DNA methylation of the selected genes was detected in plasma-cfDNA (n = 80) and in paired CTCs (n = 74). Direct comparison of DNA methylation of six genes between plasma-cfDNA and paired CTC samples (n = 70) revealed a low concordance, indicating that CTCs and cfDNA give complementary information. DNA methylation analysis of plasma-cfDNA and CTCs indicated that when at least one of these genes was methylated there was a statistically significant increase at PD compared to baseline (p = 0.031). For the first time, DNA methylation analysis in plasma-cfDNA and paired CTCs of NSCLC patients during osimertinib therapy indicated that DNA methylation of these genes could be a possible resistance mechanism.

scholarly journals Linking Cancer Stem Cell Plasticity to Therapeutic Resistance-Mechanism and Novel Therapeutic Strategies in Esophageal Cancer

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1481
Author(s):  
Chenghui Zhou ◽  
Ningbo Fan ◽  
Fanyu Liu ◽  
Nan Fang ◽  
Patrick S. Plum ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Resistance Mechanism ◽  
Therapy Resistance ◽  
Metabolic Reprogramming ◽  
Current Evidence ◽  
Mesenchymal Transition ◽  
Therapeutic Implications

Esophageal cancer (EC) is an aggressive form of cancer, including squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) as two predominant histological subtypes. Accumulating evidence supports the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. In this review, we aim to collect the current evidence on CSCs in esophageal cancer, including the biomarkers/characterization strategies of CSCs, heterogeneity of CSCs, and the key signaling pathways (Wnt/β-catenin, Notch, Hedgehog, YAP, JAK/STAT3) in modulating CSCs during esophageal cancer progression. Exploring the molecular mechanisms of therapy resistance in EC highlights DNA damage response (DDR), metabolic reprogramming, epithelial mesenchymal transition (EMT), and the role of the crosstalk of CSCs and their niche in the tumor progression. According to these molecular findings, potential therapeutic implications of targeting esophageal CSCs may provide novel strategies for the clinical management of esophageal cancer.

scholarly journals The association between MDR1 C3435T genetic polymorphism and the risk of multidrug-resistant epilepsy in Egyptian children

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Dina Salama Abd Elmagid ◽  
Maha Abdelsalam ◽  
Hend Magdy ◽  
Noha Tharwat
Keyword(s):  
Genetic Polymorphism ◽  
Sodium Valproate ◽  
Statistical Significance ◽  
Resistance Mechanism ◽  
Therapy Resistance ◽  
Multidrug Resistant ◽  
Good Prognosis ◽  
Genotype Distribution ◽  
Egyptian Children ◽  
Drug Resistant Epilepsy

Abstract Background Epilepsy is a chronic disease affecting about 2% of the population and is considered a serious neurological disease. Despite its good prognosis, 20–30% of epileptic patients were not cured of their seizures even with the many trials of antiepileptic drug (AED) therapy. The resistance mechanism is still unclear, maybe due to the effect of the genetic factors on the bioavailability of the drugs. Consequently, the association between therapy resistance and the presence of a gene called “multidrug resistance 1 (MDR1)” had been proposed. Thus, the present study aimed to understand the relationship between the genetic polymorphism of MDR1C3435T and the resistance to AEDs. Result A non-significant association was found between MDR1 C3435T single-nucleotide polymorphism (SNP) and drug-resistant epilepsy. However, there was statistical significance in the association between the drug type and the genotype distribution, in cases that were maintained on sodium valproate and MDR1C3435T genotype. Conclusion Possible involvement of the MDR1 gene C 3435T polymorphism with sodium valproate resistance clarifies the importance of genetic variability in response to the drug and may help to find novel genetic therapy for epilepsy, by targeting the biological mechanisms responsible for epilepsy in each specific individual. Future studies with bigger sample sizes and in other racial populations will be necessary.

scholarly journals Lamellipodin-RICTOR Signaling Mediates Glioblastoma Cell Invasion and Radiosensitivity Downstream of EGFR

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5337
Author(s):  
Stefanie Moritz ◽  
Matthias Krause ◽  
Jessica Schlatter ◽  
Nils Cordes ◽  
Anne Vehlow
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Unmet Need ◽  
Resistance Mechanism ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Therapy Resistance ◽  
Tumor Type ◽  
Egfr Signaling ◽  
Glioblastoma Cells ◽  
Surface Receptors

Glioblastoma is a tumor type of unmet need despite the development of multimodal treatment strategies. The main factors contributing to the poor prognosis of glioblastoma patients are diverse genetic and epigenetic changes driving glioblastoma persistence and recurrence. Complemented are these factors by extracellular cues mediated through cell surface receptors, which further aid in fostering pro-invasion and pro-survival signaling contributing to glioblastoma therapy resistance. The underlying mechanisms conferring this therapy resistance are poorly understood. Here, we show that the cytoskeleton regulator Lamellipodin (Lpd) mediates invasiveness, proliferation and radiosensitivity of glioblastoma cells. Phosphoproteome analysis identified the epidermal growth factor receptor (EGFR) signaling axis commonly hyperactive in glioblastoma to depend on Lpd. Mechanistically, EGFR signaling together with an interaction between Lpd and the Rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR) jointly regulate glioblastoma radiosensitivity. Collectively, our findings demonstrate an essential function of Lpd in the radiation response and invasiveness of glioblastoma cells. Thus, we uncover a novel Lpd-driven resistance mechanism, which adds an additional critical facet to the complex glioblastoma resistance network.

scholarly journals Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
He-Ming Zhou ◽  
Ji-Gang Zhang ◽  
Xue Zhang ◽  
Qin Li
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Patient Outcomes ◽  
Resistance Mechanism ◽  
Therapy Resistance ◽  
Resistance Mechanisms ◽  
Clinical Perspective ◽  
Differentiation Potential ◽  
Underlying Processes ◽  
Improve Patient

AbstractCancer stem cells (CSCs) show a self-renewal capacity and differentiation potential that contribute to tumor progression and therapy resistance. However, the underlying processes are still unclear. Elucidation of the key hallmarks and resistance mechanisms of CSCs may help improve patient outcomes and reduce relapse by altering therapeutic regimens. Here, we reviewed the identification of CSCs, the intrinsic and extrinsic mechanisms of therapy resistance in CSCs, the signaling pathways of CSCs that mediate treatment failure, and potential CSC-targeting agents in various tumors from the clinical perspective. Targeting the mechanisms and pathways described here might contribute to further drug discovery and therapy.

Pull-out Resistance Mechanism of Wari-kusabi Joints

2013 ◽  
Vol 59 (2) ◽  
pp. 81-89
Author(s):  
Tomoaki Soma ◽  
Masafumi Inoue ◽  
Masahiro Inayama ◽  
Hiroya Obayashi ◽  
Naoto Ando
Keyword(s):  
Resistance Mechanism ◽  
Pull Out

Symptoms Development as Tools to Differentiate Dorizontal Resistance in Sunflower

Agrotek ◽  
2018 ◽  
Vol 2 (6) ◽  
Author(s):  
Cipta Meliala ◽  
Felicity Fear ◽  
Denis Tourvieille de Labrouhe
Keyword(s):  
Downy Mildew ◽  
Natural Infection ◽  
Resistance Mechanism ◽  
Good Method ◽  
Vegetative Stage ◽  
Horizontal Resistance ◽  
Symptom Development ◽  
Plasmopara Halstedii ◽  
Controlled Conditions ◽  
Symptom Progression

Downy mildew symptoms caused by Plasmopara halstedii encountered in sunflower plantation are varied. This variation may be related to the resistance mechanism presented by plant to the invasion of the fungus. Our objectives were firstly is to evaluate symptom development after fungus race 710 inoculation on some vegetative stage of susceptible hybrid. Second objective is to evaluate the reaction some sunflower genotypes after fungus inoculation. The study was conducted under controlled conditions or under netting cages in the field. The development of downy mildew symptoms were affected by all factors studied. Shoot inoculation may present a good method to produce downy mildew symptom similar to the natural infection. Downy mildew symptom progression may be used to screen a genotype with a horizontal resistance.

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