ArticleOncotarget2017
Therapeutic sensitivity to Rac GTPase inhibition requires consequential suppression of mTORC1, AKT, and MEK signaling in breast cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed, 43 citations in OpenAlex.
- Tumor heterogeneity index from DCE-MRI for AKT-inhibition responder identification and reveals hot immune microenvironment for patients with breast cancer: a multi-omics analysis of I-SPY2 trial.Breast cancer research : BCR · 2026Article
- Article
- Review
- The PMA phorbol ester tumor promoter increases canonical Wnt signaling via macropinocytosis.eLife · 2023Article
- RAC1B function is essential for breast cancer stem cell maintenance and chemoresistance of breast tumor cells.Oncogene · 2023Article
- Structure-based design of CDC42 effector interaction inhibitors for the treatment of cancer.Cell reports · 2022Article
- RAC1 plays an essential role in estrogen receptor alpha function in breast cancer cells.Oncogene · 2021Article
- TIPE2 is a checkpoint of natural killer cell maturation and antitumor immunity.Science advances · 2021Article
- Rac inhibition as a novel therapeutic strategy for EGFR/HER2 targeted therapy resistant breast cancer.BMC cancer · 2021Article
- Targeting the cytoskeleton against metastatic dissemination.Cancer metastasis reviews · 2021Review
- Rac1, A Potential Target for Tumor Therapy.Frontiers in oncology · 2021Review
- Physiologically-Based Pharmacokinetic/Pharmacodynamic Model of MBQ-167 to Predict Tumor Growth Inhibition in Mice.Pharmaceutics · 2020Article
- Targeting Rac and Cdc42 GEFs in Metastatic Cancer.Frontiers in cell and developmental biology · 2020Review
- Subversion of Ras Small GTPases in Cutaneous Melanoma Aggressiveness.Frontiers in cell and developmental biology · 2020Review
- Methylation and serum response factor mediated in the regulation of gene ARRDC3 in breast cancer.American journal of translational research · 2020Article
- Pharmacokinetics of the Rac/Cdc42 Inhibitor MBQ-167 in Mice by Supercritical Fluid Chromatography-Tandem Mass Spectrometry.ACS omega · 2019Article
- Phosphoproteome Analysis Reveals Estrogen-ER Pathway as a Modulator of mTOR Activity Via DEPTOR.Molecular & cellular proteomics : MCP · 2019Article
- Article
- Review
- Statistical determination of synergy based on Bliss definition of drugs independence.PloS one · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Rac GTPases have oncogenic roles in cell growth, survival, and migration. We tested response to the Rac inhibitor EHT1864 in a panel of breast cancer cell lines. EHT1864-induced growth inhibition was associated with dual inhibition of the PI3K/AKT/mTORC1 and MEK/ERK pathways. Breast cancer cells harboring PIK3CA mutations or HER2 overexpression were most sensitive to Rac inhibition, suggesting that such oncogenic alterations link Rac activation with PI3K/AKT/mTORC1 and MEK/ERK signaling. Interestingly, EHT1864 decreased activation of the mTORC1 substrate p70S6K earlier than AKT inhibition, suggesting that Rac may activate mTORC1/p70S6K independently of AKT. Comparison of the growth-inhibitory profile of EHT1864 to 137 other anti-cancer drugs across 656 cancer cell lines revealed significant correlation with the p70S6K inhibitor PF-4708671. We confirmed that Rac complexes contain MEK1/2 and ERK1/2, but also contain p70S6K; these interactions were disrupted by EHT1864. Pharmacokinetic profiles revealed that EHT1864 was present in mouse plasma at concentrations effective in vitro for approximately 1 h after intraperitoneal administration. EHT1864 suppressed growth of HER2+ tumors, and enhanced response to anti-estrogen treatment in ER+ tumors. Further therapeutic development of Rac inhibitors for HER2+ and PIK3CA-mutant cancers is warranted.
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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.