ArticleOncotarget2015
The pan-PI3K inhibitor GDC-0941 activates canonical WNT signaling to confer resistance in TNBC cells: resistance reversal with WNT inhibitor.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- Rho/PAK signaling: a key driver of anthracycline and taxane resistance in breast cancer.Medical oncology (Northwood, London, England) · 2026Review
- Evolutionary conservation and cancer implications of the WNT signaling pathway.Medical oncology (Northwood, London, England) · 2025Review
- Review
- Role of EMT in drug resistance of breast cancer: molecular mechanisms and therapeutic strategies.Frontiers in oncology · 2025Review
- The mechanisms of class 1A PI3K and Wnt/β-catenin coupled signaling in breast cancer.Biochemical Society transactions · 2023Review
- Review
- Initial Phase I Safety Study of Gedatolisib plus Cofetuzumab Pelidotin for Patients with Metastatic Triple-Negative Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Wnt and PI3K/Akt/mTOR Survival Pathways as Therapeutic Targets in Glioblastoma.International journal of molecular sciences · 2022Review
- Adapalene inhibits the growth of triple-negative breast cancer cells by S-phase arrest and potentiates the antitumor efficacy of GDC-0941.Frontiers in pharmacology · 2022Article
- Cancer Stem Cells: An Ever-Hiding Foe.Experientia supplementum (2012) · 2022Article
- Molecular targets and therapeutics in chemoresistance of triple-negative breast cancer.Medical oncology (Northwood, London, England) · 2021Review
- Heparin-based hydrogel scaffolding alters the transcriptomic profile and increases the chemoresistance of MDA-MB-231 triple-negative breast cancer cells.Biomaterials science · 2020Article
- Review
- Akt1 inhibition promotes breast cancer metastasis through EGFR-mediated β-catenin nuclear accumulation.Cell communication and signaling : CCS · 2018Article
- WNT Signaling in Cardiac and Vascular Disease.Pharmacological reviews · 2018Review
- Developmental signaling pathways regulating mammary stem cells and contributing to the etiology of triple-negative breast cancer.Breast cancer research and treatment · 2016Review
- MicroRNA-3646 Contributes to Docetaxel Resistance in Human Breast Cancer Cells by GSK-3β/β-Catenin Signaling Pathway.PloS one · 2016Article
- Pharmacologic Wnt Inhibition Reduces Proliferation, Survival, and Clonogenicity of Glioblastoma Cells.Journal of neuropathology and experimental neurology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pan-PI3K inhibitors are one treatment option for triple-negative breast cancer (TNBC). However, this treatment is ineffective for unknown reasons. Here, we report that aberrant expression of wingless-type MMTV integration site family (WNT) and activated WNT signals, which crosstalk with the PI3K-AKT-mTOR signaling pathway through GSK3β, plays the most critical role in resistance to pan-PI3K inhibitors in TNBC cells. GDC-0941 is a pan-PI3K inhibitor that activates the WNT/beta-catenin pathway in TNBC cells through stimulation of WNT secretion. GDC-0941-triggered WNT/beta-catenin pathway activation was observed in MDA-MB-231 and HCC1937 cells, which are TNBC cell lines showing aberrant WNT/beta-catenin activation, and not in SKBR3 and MCF7 cells. This observation is further investigated in vivo. GDC-0941 exhibited minimal tumor inhibition in MDA-MB-231 cells, but it significantly suppressed tumor growth in HER-positive SK-BR3 cells. In vivo mechanism study revealed the activation of WNT/beta-catenin pathway by GDC-0941. A synergistic effect was observed when combined treatment with GDC-0941 and the WNT inhibitor LGK974 at low concentrations in MDA-MB-231 cells. These findings indicated that WNT pathway activation conferred resistance in TNBC cells treated with GDC-0941. This resistance may be further circumvented through combined treatment with pan-PI3K and WNT inhibitors. Future clinical trials of these two inhibitors are 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.