ArticleOncotarget2017
Inhibition of the PI3K/AKT/mTOR pathway activates autophagy and compensatory Ras/Raf/MEK/ERK signalling in prostate 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 77 papers.
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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
77 citing papers in PubMed, 124 citations in OpenAlex.
- Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial.Nature medicine · 2025Trial
- Docosahexaenoic Acid Enhances the Cytotoxic Effects of Enzalutamide and the PARP Inhibitor in Castration-Resistant Prostate Cancer Cell Lines.International journal of molecular sciences · 2026Article
- The Role of Autophagy in Cancer Evolution and Prognosis, Highlighting Its Role in PCa and Its Interaction with Apoptosis and Epigenetic Regulation by miRNAs.Medical sciences (Basel, Switzerland) · 2026Review
- Combined Omeprazole andInternational journal of molecular sciences · 2026Article
- Pharmacological mechanisms of fisetin in neurodegenerative disorders: regulation of neuroinflammatory, oxidative, and autophagic pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The FOSB-IGFBP5-IGF-1 axis: a novel regulatory pathway that suppresses prostate cancer growth.Cancer gene therapy · 2026Article
- ERRγ impedes neuroendocrine prostate cancer development.Genes & development · 2026Article
- Therapeutic effects of Melittin acupoint injection on rheumatoid arthritis through autophagy activation and PI3K/AKT/mTOR pathway inhibition.Quantitative imaging in medicine and surgery · 2026Article
- Targeting PIP5K ameliorates hepatic cancer by inhibiting PI3K/AKT and the autophagy mechanism and enhancing ROS-mediated apoptosis.Frontiers in pharmacology · 2026Article
- System analysis links SMARCD3 regulons to growth signaling and MEK inhibitor response in everolimus-resistant ER+ breast cancer cells.Cell reports. Medicine · 2025Article
- Potential repurposing of lapatinib and pazopanib as neuroprotective agents in a rat model of Huntington's disease.Inflammopharmacology · 2025Article
- Selumetinib in Adult Neurofibromatosis 1 with Plexiform Neurofibroma.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Isoquercitrin Suppresses Esophageal Squamous Cell Carcinoma (ESCC) by Inducing Excessive Autophagy and Promoting Apoptosis via the AKT/mTOR Signaling Pathway.Antioxidants (Basel, Switzerland) · 2025Article
- Autophagy: The convergence point of aging and cancer.Biochemistry and biophysics reports · 2025Review
- Multifaceted roles of melatonin in oncology: an insight into its therapeutic potential in cancer management.Inflammopharmacology · 2025Review
- The antitumor effects and apoptotic mechanism of 20(S)-Protopanaxadiol in acute myeloid leukemia.Journal of ginseng research · 2025Article
- Targeting PI3K signaling in Lung Cancer: advances, challenges and therapeutic opportunities.Journal of translational medicine · 2025Review
- Synergistic anticancer effect of CDRI-08 and abiraterone acetate against castration resistant prostate cancer targeting PI3K/Akt pathway.Iranian journal of basic medical sciences · 2025Article
- PI3K/Akt in IPF: untangling fibrosis and charting therapies.Frontiers in immunology · 2025Review
- Targeting ferroptosis for neuroprotection: potential therapeutic avenues in neurodegenerative and neuropsychiatric diseases.Frontiers in physiology · 2025Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The PI3K/AKT/mTOR pathway is frequently activated in advanced prostate cancer, due to loss of the tumour suppressor PTEN, and is an important axis for drug development. We have assessed the molecular and functional consequences of pathway blockade by inhibiting AKT and mTOR kinases either in combination or as individual drug treatments. In established prostate cancer cell lines, a decrease in cell viability and in phospho-biomarker expression was observed. Although apoptosis was not induced, a G1 growth arrest was observed in PTEN null LNCaP cells, but not in BPH1 or PC3 cells. In contrast, when the AKT inhibitor AZD7328 was applied to patient-derived prostate cultures that retained expression of PTEN, activation of a compensatory Ras/MEK/ERK pathway was observed. Moreover, whilst autophagy was induced following treatment with AZD7328, cell viability was less affected in the patient-derived cultures than in cell lines. Surprisingly, treatment with a combination of both AZD7328 and two separate MEK1/2 inhibitors further enhanced phosphorylation of ERK1/2 in primary prostate cultures. However, it also induced irreversible growth arrest and senescence.
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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.