ArticleMolecular cancer therapeutics2010
ABT-737 overcomes resistance to immunotoxin-mediated apoptosis and enhances the delivery of pseudomonas exotoxin-based proteins to the cell cytosol.
Article in Molecular cancer therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- Overcoming immunotherapy resistance in breast cancer: a novel strategy by targeting the integrated stress response.Frontiers in cell and developmental biology · 2026Review
- Antibody-Based Immunotoxins for Colorectal Cancer Therapy.Biomedicines · 2021Review
- The Effect of Novel 7-methyl-5-phenyl-pyrazolo[4,3-International journal of molecular sciences · 2020Article
- Mechanisms of Resistance to Immunotoxins ContainingBiomolecules · 2020Review
- Improved Protein Toxin Delivery Based on ATTEMPTS Systems.Current drug targets · 2018Review
- Essential role for Bim in mediating the apoptotic and antitumor activities of immunotoxins.Oncogene · 2017Article
- Clinical targeting recombinant immunotoxins for cancer therapy.OncoTargets and therapy · 2017Review
- Mechanisms of drug resistance in colon cancer and its therapeutic strategies.World journal of gastroenterology · 2016Review
- Targeting a Cancer-Specific Epitope of the Epidermal Growth Factor Receptor in Triple-Negative Breast Cancer.Journal of the National Cancer Institute · 2016Article
- Chemical Screens Identify Drugs that Enhance or Mitigate Cellular Responses to Antibody-Toxin Fusion Proteins.PloS one · 2016Article
- Mechanisms of action of therapeutic antibodies for cancer.Molecular immunology · 2015Review
- The development of immunoconjugates for targeted cancer therapy.Nature reviews. Clinical oncology · 2014Review
- ABT-737 promotes the dislocation of ER luminal proteins to the cytosol, including pseudomonas exotoxin.Molecular cancer therapeutics · 2014Article
- Cytolethal distending toxin B as a cell-killing component of tumor-targeted anthrax toxin fusion proteins.Cell death & disease · 2014Article
- Combining the antimesothelin immunotoxin SS1P with the BH3-mimetic ABT-737 induces cell death in SS1P-resistant pancreatic cancer cells.Journal of immunotherapy (Hagerstown, Md. : 1997) · 2014Article
- Antitumor effects of immunotoxins are enhanced by lowering HCK or treatment with SRC kinase inhibitors.Molecular cancer therapeutics · 2014Article
- Immunotoxins: the role of the toxin.Toxins · 2013Review
- Combination treatments with ABT-263 and an immunotoxin produce synergistic killing of ABT-263-resistant small cell lung cancer cell lines.International journal of cancer · 2013Article
- Antibody-based therapeutics for the treatment of human B cell malignancies.Current allergy and asthma reports · 2013Review
- Combination treatments with the PKC inhibitor, enzastaurin, enhance the cytotoxicity of the anti-mesothelin immunotoxin, SS1P.PloS one · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Pseudomonas exotoxin (PE)-based immunotoxins (antibody-toxin fusion proteins) have achieved frequent complete remissions in patients with hairy cell leukemia but far fewer objective responses in other cancers. To address possible mechanisms of resistance, we investigated immunotoxin activity in a model system using the colon cancer cell line, DLD1. Despite causing complete inhibition of protein synthesis, there was no evidence that an immunotoxin targeted to the transferrin receptor caused apoptosis in these cells. To address a possible protective role of prosurvival Bcl-2 proteins, the BH3-only mimetic, ABT-737, was tested alone or in combination with immunotoxins. Neither the immunotoxin nor ABT-737 alone activated caspase 3, whereas the combination exhibited substantial activation. In other epithelial cell lines, ABT-737 enhanced the cytotoxicity of PE-related immunotoxins by as much as 20-fold, but did not enhance diphtheria toxin or cycloheximide. Because PE translocates to the cytosol via the endoplasmic reticulum (ER) and the other toxins do not, ABT-737-mediated effects on the ER were investigated. ABT-737 treatment stimulated increased levels of ER stress response factor, ATF4. Because of its activity in the ER, ABT-737 might be particularly well suited for enhancing the activity of immunotoxins that translocate from the ER to the cell cytosol.
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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.