ArticleCancer cell2015
Feedback suppression of PI3Kα signaling in PTEN-mutated tumors is relieved by selective inhibition of PI3Kβ.
Article in Cancer cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 1 of them a synthesis that pooled it.
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Who cites it
148 citing papers in PubMed, 1 synthesis or guideline pooled it, 261 citations in OpenAlex.
- The prognostic value of PI3K mutational status in breast cancer: A meta-analysis.Journal of cellular biochemistry · 2018Pooled it
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- Capivasertib in combination with enzalutamide for metastatic castration resistant prostate cancer after docetaxel and abiraterone: Results from the randomized phase II RE-AKT trial.European journal of cancer (Oxford, England : 1990) · 2024Trial
- A phase II study of the dual mTOR inhibitor MLN0128 in patients with metastatic castration resistant prostate cancer.Investigational new drugs · 2018Trial
- Phase II trial of the PI3 kinase inhibitor buparlisib (BKM-120) with or without enzalutamide in men with metastatic castration resistant prostate cancer.European journal of cancer (Oxford, England : 1990) · 2017Trial
- PI3K signaling in breast cancer: therapeutic advances versus adaptive resistance.The Journal of clinical investigation · 2026Review
- PIK3CA mutations and PI3K isoform expression define prognostic signatures in ovarian clear cell carcinoma.Archives of gynecology and obstetrics · 2026Article
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- Cooperative Roles of Class IA PI3K Isoforms in Translocation-Related Sarcoma Cell Survival and Proliferation.Cancer research communications · 2026Article
- Synergistic Efficacy of Gedatolisib and Darolutamide in Prostate Cancer to Overcome Resistance to Androgen-Targeted Therapy.International journal of molecular sciences · 2025Article
- Phosphatidylinositol 3-kinase and mechanistic target of rapamycin dualinhibitor, VDC597, as a therapeutic agent for canine osteosarcoma.The Journal of pharmacology and experimental therapeutics · 2025Article
- Targeting KRAS in colorectal cancer (Review).Molecular and clinical oncology · 2025Review
- The role of the striatin family proteins in hippo signaling and cellular regulation.Cell & bioscience · 2025Article
- A novel bone metastasis-related gene signature for predicting prognosis, anti-androgen resistance, and drug choice in prostate cancer.Journal of bone oncology · 2025Article
- Review
- The role of FAM111B in the malignant progression and molecular regulation of human glioma through the PI3K/Akt pathway.Chinese neurosurgical journal · 2025Article
- Article
- Use of metabolic imaging to monitor heterogeneity of tumour response following therapeutic mTORC1/2 pathway inhibition.Disease models & mechanisms · 2025Article
- Article
- Molecular mechanisms of PI3K isoform dependence in embryonic growth.Journal of the Turkish German Gynecological Association · 2024Article
88 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
In PTEN-mutated tumors, we show that PI3Kα activity is suppressed and PI3K signaling is driven by PI3Kβ. A selective inhibitor of PI3Kβ inhibits the Akt/mTOR pathway in these tumors but not in those driven by receptor tyrosine kinases. However, inhibition of PI3Kβ only transiently inhibits Akt/mTOR signaling because it relieves feedback inhibition of IGF1R and other receptors and thus causes activation of PI3Kα and a rebound in downstream signaling. This rebound is suppressed and tumor growth inhibition enhanced with combined inhibition of PI3Kα and PI3Kβ. In PTEN-deficient models of prostate cancer, this effective inhibition of PI3K causes marked activation of androgen receptor activity. Combined inhibition of both PI3K isoforms and androgen receptor results in major tumor regressions.
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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.