ArticleMolecular pharmacology2012
Lapatinib and obatoclax kill breast cancer cells through reactive oxygen species-dependent endoplasmic reticulum stress.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- ER stress as a trigger of UPR and ER-phagy in cancer growth and spread.Frontiers in oncology · 2022Pooled it
- Photothermal therapy triggering organelle stress and metabolic reprogramming to potentiate antitumor immunity.Frontiers in immunology · 2026Review
- Promoting reactive oxygen species accumulation to overcome tyrosine kinase inhibitor resistance in cancer.Cancer cell international · 2024Review
- Eupalinolide B inhibits hepatic carcinoma by inducing ferroptosis and ROS-ER-JNK pathway.Acta biochimica et biophysica Sinica · 2022Article
- Mechanism and effect of stress granule formation in cancer and its potential roles in breast cancer therapy.Genes & diseases · 2022Review
- Article
- Identification of lapatinib sensitivity-related genes by integrative functional module analysis.Translational cancer research · 2020Article
- Treatment of cancer cells with Lapatinib negatively regulates general translation and induces stress granules formation.PloS one · 2020Article
- EP300 and SIRT1/6 Co-Regulate Lapatinib Sensitivity Via Modulating FOXO3-Acetylation and Activity in Breast Cancer.Cancers · 2019Article
- Glucose-6-phosphate dehydrogenase blockade potentiates tyrosine kinase inhibitor effect on breast cancer cells through autophagy perturbation.Journal of experimental & clinical cancer research : CR · 2019Article
- Review
- The Unfolded Protein Response in Breast Cancer.Cancers · 2018Review
- PTK6 regulates growth and survival of endocrine therapy-resistant ER+ breast cancer cells.NPJ breast cancer · 2017Article
- Article
- Smac mimetic LCL161 overcomes protective ER stress induced by obatoclax, synergistically causing cell death in multiple myeloma.Oncotarget · 2016Article
- Everolimus enhances cellular cytotoxicity of lapatinib via the eukaryotic elongation factor-2 kinase pathway in nasopharyngeal carcinoma cells.OncoTargets and therapy · 2016Article
- Lapatinib induces autophagic cell death and differentiation in acute myeloblastic leukemia.OncoTargets and therapy · 2016Article
- Article
- Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP.Oncotarget · 2015Article
- Sorafenib/regorafenib and lapatinib interact to kill CNS tumor cells.Journal of cellular physiology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Previous studies showed that lapatinib and obatoclax interact in a greater-than-additive fashion to cause cell death and do so through a toxic form of autophagy. The present studies sought to extend our analyses. Lapatinib and obatoclax killed multiple tumor cell types, and cells lacking phosphatase and tensin homolog (PTEN) function were relatively resistant to drug combination lethality; expression of PTEN in PTEN-null breast cancer cells restored drug sensitivity. Coadministration of lapatinib with obatoclax elicited autophagic cell death that was attributable to the actions of mitochondrial reactive oxygen species. Wild-type cells but not mitochondria-deficient rho-zero cells were radiosensitized by lapatinib and obatoclax treatment. Activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH(2)-terminal kinase 1/2 (JNK1/2) by the drug combination was enhanced by radiation, and signaling by p38 MAPK and JNK1/2 promoted cell killing. In immunohistochemical analyses, the autophagosome protein p62 was determined to be associated with protein kinase-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1, as well as with binding immunoglobulin protein/78-kDa glucose-regulated protein, in drug combination-treated cells. Knockdown of PERK suppressed drug-induced autophagy and protected tumor cells from the drug combination. Knockdown of PERK suppressed the reduction in Mcl-1 expression after drug combination exposure, and overexpression of Mcl-1 protected cells. Our data indicate that mitochondrial function plays an essential role in cell killing by lapatinib and obatoclax, as well as radiosensitization by this drug combination.
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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.