ArticleCell cycle (Georgetown, Tex.)2012
Combined inhibition of Wee1 and Hsp90 activates intrinsic apoptosis in cancer cells.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed, 23 citations in OpenAlex.
- PU-H71 (NSC 750424): a molecular masterpiece that targets HSP90 in cancer and beyond.Frontiers in pharmacology · 2024Review
- Synthetic and Medicinal Chemistry Approaches Toward WEE1 Kinase Inhibitors and Its Degraders.ACS omega · 2023Review
- Article
- Wee1 Kinase: A Potential Target to Overcome Tumor Resistance to Therapy.International journal of molecular sciences · 2021Review
- Post-translational modifications of Hsp90 and translating the chaperone code.The Journal of biological chemistry · 2020Review
- The Multiple Roles and Therapeutic Potential of Molecular Chaperones in Prostate Cancer.Cancers · 2019Review
- Targeting heat-shock protein 90 with ganetespib for molecularly targeted therapy of gastric cancer.Cell death & disease · 2015Article
- Up-regulation of mitochondrial chaperone TRAP1 in ulcerative colitis associated colorectal cancer.World journal of gastroenterology · 2014Article
- Wee1 kinase as a target for cancer therapy.Cell cycle (Georgetown, Tex.) · 2013Review
- Contributions of co-chaperones and post-translational modifications towards Hsp90 drug sensitivity.Future medicinal chemistry · 2013Review
- Wee1-Hsp90 inhibitor combination treatment: molecular therapy with potentially broad applicability.Cell cycle (Georgetown, Tex.) · 2012Article
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Heat shock protein 90 (Hsp90) is an essential, evolutionarily conserved molecular chaperone. Cancer cells rely on Hsp90 to chaperone mutated and/or activated oncoproteins, and its involvement in numerous signaling pathways makes it an attractive target for drug development. Surprisingly, however, the impact of Hsp90 inhibitors on cancer cells is frequently cytostatic in nature, and efforts to enhance the antitumor activity of Hsp90 inhibitors in the clinic remain a significant challenge. In agreement with previous data obtained using Wee1 siRNA, we show that dual pharmacologic inhibition of Wee1 tyrosine kinase and Hsp90 causes cancer cells to undergo apoptosis in vitro and in vivo. Gene expression profiling revealed that induction of the intrinsic apoptotic pathway by this drug combination coincided with transcriptional downregulation of Survivin and Wee1, an outcome not seen in cells treated separately with either agent. At the translational level, expression of these two proteins, as well as activated Akt, was completely abrogated. These data support the hypothesis that Wee1 inhibition sensitizes cancer cells to Hsp90 inhibitors; they establish combined Wee1/Hsp90 inhibition as a novel therapeutic strategy; and they provide a mechanistic rationale for enhancing the pro-apoptotic activity of Hsp90 inhibitors.
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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.