ArticleOncogenesis2017
Vertical inhibition of the PI3K/Akt/mTOR pathway is synergistic in breast cancer.
Article in Oncogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed.
- GATRSyn: Advancing Anticancer Drug Synergy Prediction Through Graph Attention Networks and Transformer-based Feature Re-embedding.Interdisciplinary sciences, computational life sciences · 2026Article
- Transcription co-inhibition alters drug resistance evolution and enhances Mycobacterium tuberculosis clearance from granulomas.Nature microbiology · 2026Article
- A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer.Journal of advanced research · 2023Review
- Drug Repurposing to Circumvent Immune Checkpoint Inhibitor Resistance in Cancer Immunotherapy.Pharmaceutics · 2023Review
- Extensive review on breast cancer its etiology, progression, prognostic markers, and treatment.Medical oncology (Northwood, London, England) · 2023Review
- Ran GTPase and Its Importance in Cellular Signaling and Malignant Phenotype.International journal of molecular sciences · 2023Review
- MicroRNA miR-627-5p restrains pulmonary artery smooth muscle cell dysfunction by targeting MAP 2 K4 and PI3K/AKT signaling.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2022Article
- Co-targeting CDK2 and CDK4/6 overcomes resistance to aromatase and CDK4/6 inhibitors in ER+ breast cancer.NPJ precision oncology · 2022Article
- CircSEMA4B inhibits the progression of breast cancer by encoding a novel protein SEMA4B-211aa and regulating AKT phosphorylation.Cell death & disease · 2022Article
- PD-L1/pS6 in Circulating Tumor Cells (CTCs) during Osimertinib Treatment in Patients with Non-Small Cell Lung Cancer (NSCLC).Biomedicines · 2022Article
- Article
- AAV expressing an mTOR-inhibiting siRNA exhibits therapeutic potential in retinal vascular disorders by preserving endothelial integrity.FEBS open bio · 2022Article
- The Discovery of New Drug-Target Interactions for Breast Cancer Treatment.Molecules (Basel, Switzerland) · 2021Article
- Emergence of mTOR mutation as an acquired resistance mechanism to AKT inhibition, and subsequent response to mTORC1/2 inhibition.NPJ precision oncology · 2021Article
- Phase Ib Dose Expansion and Translational Analyses of Olaparib in Combination with Capivasertib in Recurrent Endometrial, Triple-Negative Breast, and Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- New strategies for targeting kinase networks in cancer.The Journal of biological chemistry · 2021Review
- Halofuginone, a promising drug for treatment of pulmonary hypertension.British journal of pharmacology · 2021Article
- Article
- AKT signaling restrains tumor suppressive functions of FOXO transcription factors and GSK3 kinase in multiple myeloma.Blood advances · 2020Article
- Profound Reprogramming towards Stemness in Pancreatic Cancer Cells as Adaptation to AKT Inhibition.Cancers · 2020Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Deregulation and activation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian (or mechanistic) target of rapamycin (mTOR) pathway have a major role in proliferation and cell survival in breast cancer. However, as single agents, mTOR inhibitors have had modest antitumor efficacy. In this study, we evaluated the effects of vertical inhibition of mTOR and Akt in breast cancer cell lines and xenografts. We assessed the effects of mTOR inhibitor rapamycin and Akt inhibitor MK-2206, given as single drugs or in combination, on cell signaling, cell proliferation and apoptosis in a panel of cancer cell lines in vitro. The antitumor efficacy was tested in vivo. We demonstrated that MK-2206 inhibited Akt phosphorylation, cell proliferation and apoptosis in a dose-dependent manner in breast cancer cell lines. Rapamycin inhibited S6 phosphorylation and cell proliferation, and resulted in lower levels of apoptosis induction. Furthermore, the combination treatment inhibited phosphorylation of Akt and S6, synergistically inhibited proliferation and induced apoptosis with a higher efficacy. In vivo combination inhibited tumor growth more than either agent alone. Our data suggest that a combination of Akt and mTOR inhibitors have greater antitumor activity in breast cancer cells, which may be a viable approach to treat patients.
Identifiers
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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.