Resistance Studies in Lung Cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA276487 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In depth label free quantitative mass spectrometry based proteomics for identification of potential biomarkers of drug resistance in lung cancer.
2023-03-10 | PXD036996 | Pride
Project description:Lung cancer is the leading cause of cancer related deaths, worldwide. Fibroblast growth factor receptor 1 (FGFR1) gene amplification is one of the most prominent and potentially targetable genetic alterations in squamous cell lung cancer (SQCLC). Highly selective tyrosine kinase inhibitors have been developed to target FGFR1, however, resistance mechanisms originally existing in patients or acquired throughout treatment have limited treatment efficiency in clinical trials, so far. In this study, we performed a wide-scale phosphoproteomic mass spectrometry analysis to explore signaling pathways that lead to FGFR1 inhibition resistance in lung cancer cells with intrinsic, induced and mutational resistance. We identified a CD44/AKT signaling axis as a new and common mechanism of resistance to FGFR1 inhibition in lung cancer. Co-inhibition of AKT or CD44 synergistically sensitized intrinsic and induced resistant cells to FGFR1 inhibition. Furthermore, strong CD44 expression was significantly correlated to AKT activation in squamous cell lung cancer patients. Collectively, our phosphoproteomic analysis of FGFR1 inhibitor resistant lung cancer cells promotes a large data library of resistance associated phosphorylation patterns and proposes a common resistance pathway consisting of CD44 and AKT activation. Examination of CD44/AKT activation could help to predict response to FGFR1 inhibition and combination with AKT inhibitors might path the way for an effective therapy of FGFR1 dependent lung cancer patients in case of treatment resistance.
2022-08-12 | PXD025389 | Pride
Project description:Standard chemotherapy for lung cancer often leads to drug resistance, posing a significant clinical challenge. A major mechanism of resistance is overexpression of P-glycoprotein (P-gp), encoded by the human ATP-binding cassette subfamily B member 1 (hABCB1) gene, functioning as a drug efflux transporter. In this study, we aimed to investigate the dual role of hABCB1 overexpression in mediating resistance to chemotherapy and natural killer (NK) cell-mediated cytotoxicity in lung cancer.
2025-01-06 | MSV000096780 | MassIVE
Project description:<p>The purpose of the study was to compare gene expression profiles from a cohort of crizotinib-resistant ALK-rearranged lung tumors and a cohort of treatment-naive ALK-rearranged lung tumors. Expression profiles were generated by RNA-seq. In parallel, gene expression profiles were obtained from ALK-rearranged lung cancer cell lines in the presence or absence of the ALK inhibitor TAE684. Gene expression profiles were also obtained from ALK-rearranged cells ectopically expressing genes associated with ALK inhibitor resistance that were identified from a functional genetic study.</p>
| phs000855 | dbGaP
Project description:Purpose: To characterize microRNA signatures for tolerance, persistence and resistance to EGFR tyrosine kinase inhibitors (TKIs) in human lung cancer. Methods: microRNA profiles of gefitinib- and osimertinib-tolerant cells in PC9 and HCC827 cells were generated by deep microRNA sequencing using Illumina. In addition, microRNA profiles of PC9 subpopulations cells with characterizations of persistence and resistance to gefitinib were generated by deep microRNA sequencing. The mappable reads were aligned to the human genome and miRbase using Bowtie. Results: We identified a specific microRNA profile distinguishing tolerance, persistence and resistance to gefitinib or osimertinib from parental human lung cancer cells with mutated EGFR. The expressions of those microRNAs in lung cancer cells were validated by qRT-PCR. Functionally, knocking down top-upregulated microRNAs reduced the tolerance, persistence and resistance to gefitinib or osimertinib in those tolerant and resistant cells. Conversely, overexpression of those microRNAs enhanced the tolerance and resistance to EGFR inhibition in cells sensitive to gefitinib and osimertinib. Conclusions: Our work identifies a panel of microRNAs that mediate EGFR-TKI tolerance and resistance in lung cancer. Our study provides potential non-coding targets to improve the efficacy of EGFR-TKIs therapy in cancer pagtients.
2018-01-11 | GSE103352 | GEO
Project description:Targeted tyrosine kinase inhibitors (TKIs) play a crucial role in the treatment of lung cancer; however, nearly all patients face the challenge of TKI resistance. Unraveling the molecular mechanisms of TKI resistance and effectively addressing it is a pressing clinical issue. We have successfully established a third-generation TKI-resistant lung cancer cell line and organoids, and identified batatasin alkaloid from 302 traditional Chinese medicines as capable of effectively overcoming osimertinib resistance. Our scientific hypothesis posits that batatasin alkaloid improves osimertinib resistance by modulating ACSL1 to influence lipid peroxidation-induced ferroptosis. This project aims to utilize various lung cancer models to elucidate the relationship between osimertinib resistance and ferroptosis in lung cancer, uncover the specific molecular mechanisms by which batatasin alkaloid regulates ACSL1, and explore the feasibility of batatasin alkaloid in improving osimertinib resistance. This project will unveil novel molecular mechanisms of TKI resistance in lung cancer and explore the application of traditional Chinese medicine in overcoming resistance to targeted therapy for lung cancer.
2025-08-06 | GSE276807 | GEO
Project description:Mechanisms of drugs-resistance in small cell lung cancer
| PRJNA706414 | ENA
Project description:Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) remains a major clinical challenge in the targeted therapy of non-small cell lung cancer (NSCLC), yet its underlying mechanisms are poorly understood. The tumor microenvironment (TME), which provides a supportive niche for cancer cell survival and progression, plays a pivotal role in NSCLC drug resistance. Our preliminary studies revealed that activated cancer-associated fibroblasts (CAFs) in the TME induce EGFR-TKI resistance in lung cancer cells by secreting neuregulin-1 (NRG1). Further investigations identified STAT3 as a key regulator of CAF activation and secretory function. We thus hypothesize that inhibiting STAT3 activation may block CAF-mediated secretion, thereby reversing EGFR-TKI resistance in lung cancer.
2025-05-26 | PXD064318 |
Project description:Anoikis (detachment-induced cell death) is a specific type of programmed cell death which occurs in response to the loss of the correct extracellular matrix connections. Anoikis resistance is an important mechanism in cancer invasiveness and metastatic behavior. Autophagy, on the other hand, involves the degradation of damaged organelles and the recycling of misfolded proteins and intracellular components. However, the intersection of these two cellular responses in lung cancer cells has not been extensively studied. Here, we identified that upon matrix deprivation, the lymphocyte lineage-specific Ets transcription factor SPIB was activated and directly enhanced SNAP47 transcription in certain lung cancer cells. Loss of attachment-induced autophagy significantly increased anoikis resistance by SPIB activation. Consistent with this function, SPIB depletion by short hairpin RNA abrogated SNAP47 transcriptional activation upon matrix deprivation. Therefore, these data delineate an important role of SPIB in autophagy-mediated anoikis resistance in lung cancer cells. Accordingly, these findings suggest that manipulating SPIB-regulated pathways in vivo and evaluating the impact of anoikis resistance warrant further investigation.
2019-03-11 | GSE125561 | GEO
Project description:Activating mutations of EGFR have been characterized as important mechanisms for carcinogenesis in a subset of EGFR-dependent non-small cell lung cancers (NSCLC). EGFR tyrosine kinase inhibitors (TKI), such as erlotinib and gefitinib, have dramatic clinical effects on EGFR-addicted lung cancers and are used as first-line therapy for EGFR-mutant tumors. However, eventually all tumors acquire secondary resistance to the drugs and progress. We established a model to better understand mechanisms of acquired resistance. NCI- HCC827 cells are EGFR-mutant and highly erlotinib-sensitive. In this study we exposed HCC827 cells to increasing concentrations of erlotinib and two highly erlotinib-resistant subclones were developed (ER3 and T15-2). In these subclones no acquired alterations of EGFR or MET were found. We hereby performed a gene expression microarray studies to understand changes that might explain mechanisms of resistance. Through these studies we demonstrated in one resistant clone (ER3) overexpression of AXL, a tyrosine kinase implicated in imatinib and lapatinib resistance. Gene expression profilings were measured in NSCLC cell line HCC827 and two erlotinib-resistant HCC827-originated sublines ER3 and T15-2.
2012-05-29 | E-GEOD-38310 | biostudies-arrayexpress