ArticleCancer research2008
Targeting endoplasmic reticulum stress and Akt with OSU-03012 and gefitinib or erlotinib to overcome resistance to epidermal growth factor receptor inhibitors.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 58 citations in OpenAlex.
- Oncoprotein LAMTOR5-mediated CHOP silence via DNA hypermethylation and miR-182/miR-769 in promotion of liver cancer growth.Acta pharmacologica Sinica · 2024Article
- 6-Shogaol Overcomes Gefitinib Resistance via ER Stress in Ovarian Cancer Cells.International journal of molecular sciences · 2023Article
- Selenium Yeast and Fish Oil Combination Diminishes Cancer Stem Cell Traits and Reverses Cisplatin Resistance in A549 Sphere Cells.Nutrients · 2022Article
- Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer.Nature reviews. Cancer · 2022Review
- Development of a new EGFR antibody antagonist which exhibits potential biological effects against laryngeal cancer.Annals of translational medicine · 2021Article
- OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo.Drug design, development and therapy · 2021Article
- Article
- Urine Sample-Derived Cerebral Organoids Suitable for Studying Neurodevelopment and Pharmacological Responses.Frontiers in cell and developmental biology · 2020Article
- Targeting the unfolded protein response in head and neck and oral cavity cancers.Experimental cell research · 2019Review
- Structural and functional insights into theeLife · 2019Article
- GIV/Girdin promotes cell survival during endoplasmic reticulum stress.Molecular and cellular biochemistry · 2019Article
- Stress and interferon signalling-mediated apoptosis contributes to pleiotropic anticancer responses induced by targeting NGLY1.British journal of cancer · 2018Article
- Combination Strategies Using EGFR-TKi in NSCLC Therapy: Learning from the Gap between Pre-Clinical Results and Clinical Outcomes.International journal of biological sciences · 2018Review
- Potassium as a pluripotency-associated element identified through inorganic element profiling in human pluripotent stem cells.Scientific reports · 2017Article
- Needle-Free Delivery of Acetalated Dextran-Encapsulated AR-12 Protects Mice from Francisella tularensis Lethal Challenge.Antimicrobial agents and chemotherapy · 2016Article
- A Combination of Two Receptor Tyrosine Kinase Inhibitors, Canertinib and PHA665752 Compromises Ovarian Cancer Cell Growth in 3D Cell Models.Oncology and therapy · 2016Article
- GRP78/Dna K Is a Target for Nexavar/Stivarga/Votrient in the Treatment of Human Malignancies, Viral Infections and Bacterial Diseases.Journal of cellular physiology · 2015Article
- Matched miRNA and mRNA signatures from an hESC-based in vitro model of pancreatic differentiation reveal novel regulatory interactions.Journal of cell science · 2013Article
- OSU-03012 sensitizes breast cancers to lapatinib-induced cell killing: a role for Nck1 but not Nck2.BMC cancer · 2013Article
- RAF1-MEK1-ERK/AKT axis may confer NSCLC cell lines resistance to erlotinib.International journal of clinical and experimental pathology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Preexisting and acquired resistance to epidermal growth factor receptor (EGFR) inhibitors limits their clinical usefulness in patients with advanced non-small cell lung cancer (NSCLC). This study characterizes the efficacy and mechanisms of the combination of gefitinib or erlotinib with OSU-03012, a celecoxib-derived antitumor agent, to overcome EGFR inhibitor resistance in three NSCLC cell lines, H1155, H23, and A549. The OSU-03012/EGFR inhibitor combination induced pronounced apoptosis in H1155 and H23 cells, but not in A549 cells, suggesting a correlation between drug sensitivity and basal phospho-Akt levels independently of EGFR expression status. Evidence indicates that this combination facilitates apoptosis through both Akt signaling inhibition and up-regulation of endoplasmic reticulum (ER) stress-induced, GADD153-mediated pathways. For example, ectopic expression of constitutively active Akt significantly attenuated the inhibitory effect on cell survival, and small interfering RNA-mediated knockdown of GADD153 protected cells from undergoing apoptosis in response to drug cotreatments. Furthermore, the OSU-03012/EGFR inhibitor combination induced GADD153-mediated up-regulation of death receptor 5 expression and subsequent activation of the extrinsic apoptosis pathway. It is noteworthy that the ER stress response induced by this combination was atypical in that the cytoprotective pathway was not engaged. In addition, in vivo suppression of tumor growth and modulation of intratumoral biomarkers were observed in a H1155 tumor xenograft model in nude mice. These data suggest that the concomitant modulation of Akt and ER stress pathways with the OSU-03012/EGFR inhibitor combination represents a unique approach to overcoming EGFR inhibitor resistance in NSCLC and perhaps other types of cancer with elevated basal Akt activities.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.