ArticleBMC cancer2021
Rac inhibition as a novel therapeutic strategy for EGFR/HER2 targeted therapy resistant breast cancer.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06075810 (A Phase 1 Open-Label, First-in-Human Trial of Oral MBQ-167 as Single Agent in Participants With Advanced Breast Cancer), which is not on this map. Cited by 12 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.
A Phase 1 Open-Label, First-in-Human Trial of Oral MBQ-167 as Single Agent in Participants With Advanced Breast Cancer
Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- M6 Metabolite Contributes to the Efficacy of the Rac/Cdc42 Inhibitor MBQ-167 in Metastatic Breast Cancer.Molecular cancer therapeutics · 2026Article
- Rho GTPases in cancer resistance: mechanisms, vulnerabilities, and therapeutic opportunities.Biochemical Society transactions · 2026Review
- Non-coding RNAs (ncRNAs)-mediated high expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) correlates with poor prognosis and tumor immune infiltration of liver hepatocellular carcinoma.Translational cancer research · 2026Article
- Novel Inhibition of Central Carbon Metabolism Pathways by Rac and CDC42 inhibitor MBQ167 and Paclitaxel.Molecular cancer therapeutics · 2024Article
- Targeting guanine nucleotide exchange factors for novel cancer drug discovery.Expert opinion on drug discovery · 2024Review
- Statins as anti-tumor agents: A paradigm for repurposed drugs.Cancer reports (Hoboken, N.J.) · 2024Review
- The Rac1-inhibitor EHop-016 attenuates AML cell migration and enhances the efficacy of daunorubicin in MOLM-13 transplanted zebrafish larvae.Translational oncology · 2024Article
- Diosgenin and Monohydroxy Spirostanol fromPharmaceuticals (Basel, Switzerland) · 2023Article
- Rac and Cdc42 inhibitors reduce macrophage function in breast cancer preclinical models.Frontiers in oncology · 2023Article
- Characterization of Novel Derivatives of MBQ-167, an inhibitor of the GTP-binding proteins Rac/Cdc42.Cancer research communications · 2022Article
- Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder.Biomedicines · 2022Review
- Carboranes as unique pharmacophores in antitumor medicinal chemistry.Molecular therapy oncolytics · 2022Review
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 1 institution in 1 country.
Funding
Abstract
backgroundEven though targeted therapies are available for cancers expressing oncogenic epidermal growth receptor (EGFR) and (or) human EGFR2 (HER2), acquired or intrinsic resistance often confounds therapy success. Common mechanisms of therapy resistance involve activating receptor point mutations and (or) upregulation of signaling downstream of EGFR/HER2 to Akt and (or) mitogen activated protein kinase (MAPK) pathways. However, additional pathways of resistance may exist thus, confounding successful therapy.
methodsTo determine novel mechanisms of EGFR/HER2 therapy resistance in breast cancer, gefitinib or lapatinib resistant variants were created from SKBR3 breast cancer cells. Syngenic therapy sensitive and resistant SKBR3 variants were characterized for mechanisms of resistance by mammosphere assays, viability assays, and western blotting for total and phospho proteins.
resultsGefitinib and lapatinib treatments reduced mammosphere formation in the sensitive cells, but not in the therapy resistant variants, indicating enhanced mesenchymal and cancer stem cell-like characteristics in therapy resistant cells. The therapy resistant variants did not show significant changes in known therapy resistant pathways of AKT and MAPK activities downstream of EGFR/HER2. However, these cells exhibited elevated expression and activation of the small GTPase Rac, which is a pivotal intermediate of GFR signaling in EMT and metastasis. Therefore, the potential of the Rac inhibitors EHop-016 and MBQ-167 to overcome therapy resistance was tested, and found to inhibit viability and induce apoptosis of therapy resistant cells.
conclusionsRac inhibition may represent a viable strategy for treatment of EGFR/HER2 targeted therapy resistant breast cancer.
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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.