ArticleLeukemia2006
Targeting Hsp90 by 17-AAG in leukemia cells: mechanisms for synergistic and antagonistic drug combinations with arsenic trioxide and Ara-C.
Article in Leukemia, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 42 citations in OpenAlex.
- Smart Nanofiber Mesh with Locally Sustained Drug Release Enabled Synergistic Combination Therapy for Glioblastoma.Nanomaterials (Basel, Switzerland) · 2023Article
- Combination effects of capecitabine, irinotecan and 17-AAG on colorectal cancer cell line (HT-29).Annals of medicine and surgery (2012) · 2022Article
- HSP90α Mediates Sorafenib Resistance in Human Hepatocellular Carcinoma by Necroptosis Inhibition under Hypoxia.Cancers · 2021Article
- The HSP90 inhibitor, 17AAG, protects the intestinal stem cell niche and inhibits graft versus host disease development.Oncogene · 2016Article
- In vitro discovery of promising anti-cancer drug combinations using iterative maximisation of a therapeutic index.Scientific reports · 2015Article
- The presence of wild type p53 in hematological cancers improves the efficacy of combinational therapy targeting metabolism.Oncotarget · 2015Article
- Article
- Multimodal delivery of irinotecan from microparticles with two distinct compartments.Journal of controlled release : official journal of the Controlled Release Society · 2013Article
- Hsp90 inhibitors and drug resistance in cancer: the potential benefits of combination therapies of Hsp90 inhibitors and other anti-cancer drugs.Biochemical pharmacology · 2012Review
- Synergistic Apoptosis-Inducing Antileukemic Effects of Arsenic Trioxide and Mucuna macrocarpa Stem Extract in Human Leukemic Cells via a Reactive Oxygen Species-Dependent Mechanism.Evidence-based complementary and alternative medicine : eCAM · 2012Article
- Phase I and pharmacological study of cytarabine and tanespimycin in relapsed and refractory acute leukemia.Haematologica · 2011Article
- Facilitating Akt clearance via manipulation of Hsp70 activity and levels.The Journal of biological chemistry · 2010Article
- Mechanisms of drug combinations: interaction and network perspectives.Nature reviews. Drug discovery · 2009Review
- Synergism between arsenic trioxide and heat shock protein 90 inhibitors on signal transducer and activator of transcription protein 3 activity--pharmacodynamic drug-drug interaction modeling.Clinical cancer research : an official journal of the American Association for Cancer Research · 2007Article
- New therapeutic strategies for the treatment of acute lymphoblastic leukaemia.Nature reviews. Drug discovery · 2007Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
17-Allylamino-17-demethoxygeldanamycin (17-AAG) is a new anticancer agent currently in clinical trials. The ability of 17-AAG to abrogate the function of heat-shock protein Hsp90 and modulate cellular sensitivity to anticancer agents has prompted recent research to use this compound in drug combination therapy. Here we report that 17-AAG has striking opposite effects on the activity of arsenic trioxide (ATO) and ara-C. Combination of 17-AAG with ATO exhibited a synergistic effect in leukemia cells, whereas coincubation of 17-AAG and ara-C showed antagonistic activity. Mechanistic studies revealed that ATO exerted cytotoxic action by reactive oxygen species generation, and activated Akt survival pathway. 17-AAG abrogated Akt activation and enhanced the activity of ATO. In contrast, treatment of leukemia cells with 17-AAG caused a G1 arrest, a decrease in DNA synthesis and reduced ara-C incorporation into DNA, leading to antagonism. The ability of 17-AAG to enhance the antileukemia activity of ATO was further demonstrated in primary leukemia cells isolated from patients with acute myeloid leukemia and chronic lymphocytic leukemia, including cells from refractory patients. Our data suggest that combination of 17-AAG and ATO may be an effective therapeutic regimen. Caution should be exercised in using 17-AAG together with ara-C, as their combination effects are schedule dependent.
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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.