ArticleProceedings of the National Academy of Sciences of the United States of America2008
PTEN-deficient cancers depend on PIK3CB.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 309 papers.
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Who cites it
309 citing papers in PubMed, 549 citations in OpenAlex.
- PIK3CB Inhibitor GSK2636771 in Cancers WithJCO precision oncology · 2025Trial
- AZD8186 in Combination With Paclitaxel in Patients With Advanced Gastric Cancer: Results From a Phase Ib/II Study (KCSG ST18-20).The oncologist · 2023Trial
- Phase II Study of Taselisib inJCO precision oncology · 2022Trial
- Target and Agent Prioritization for the Children's Oncology Group-National Cancer Institute Pediatric MATCH Trial.Journal of the National Cancer Institute · 2017Trial
- PI3K signaling in breast cancer: therapeutic advances versus adaptive resistance.The Journal of clinical investigation · 2026Review
- Loss of the tumor suppressor PTEN activates cell-intrinsic interferon signaling to drive immune resistance.Genes & development · 2026Article
- Network Toxicology and In Vivo Studies Reveal the Toxicity and Mechanisms of Tributyl Citrate Carried by Microplastics in Promoting Colitis-to-Tumorigenesis Transformation.Environment & health (Washington, D.C.) · 2026Article
- Cooperative Roles of Class IA PI3K Isoforms in Translocation-Related Sarcoma Cell Survival and Proliferation.Cancer research communications · 2026Article
- PTEN Loss Promotes PI3Kβ Phosphorylation and EPHA2/SRC/p-PI3KβY962 Complex Assembly to Drive Tumorigenesis.Cancer discovery · 2026Article
- EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.Nature communications · 2026Article
- Mesenchymal stem cells ameliorate Sjögren disease by suppressing B cells through the Pik3cb/Akt/mTOR pathway.Frontiers in immunology · 2026Article
- Article
- Novel role for PI3Kβ in placental function through regulation of system A amino acid transporter expression, associated with embryonic lethality.Cellular and molecular life sciences : CMLS · 2025Article
- PI3Kγ in Tumour Inflammation: Bridging Immune Response and Cancer Progression-A Mini-Review.Immunology · 2025Review
- Loss of the tumor suppressor PTEN activates cell-intrinsic interferon signaling to drive immune resistance.bioRxiv : the preprint server for biology · 2025Article
- Dual EZH1/2 inhibition enhances DNMT inhibitor efficacy in colon cancer through targeting H3K27me1.bioRxiv : the preprint server for biology · 2025Article
- A phase I study of AZD8186 in combination with docetaxel in patients with PTEN-mutated or PIK3CB-mutated advanced solid tumors.ESMO open · 2025Article
- PI3Kβ moonlights as a protein kinase: driving fatty acid metabolism and histone acetylation in cancer.Cancer biology & medicine · 2025Article
- Review
- The interplay between FOXO3 and FOXM1 influences sensitivity to AKT inhibition in PIK3CA and PIK3CA/PTEN altered estrogen receptor positive breast cancer.NPJ breast cancer · 2025Article
249 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deregulation of the PI3K signaling pathway is observed in many human cancers and occurs most frequently through loss of PTEN phosphatase tumor suppressor function or through somatic activating mutations in the Class IA PI3K, PIK3CA. Tumors harboring activated p110alpha, the protein product of PIK3CA, require p110alpha activity for growth and survival and hence are expected to be responsive to inhibitors of its lipid kinase activity. Whether PTEN-deficient cancers similarly depend on p110alpha activity to sustain activation of the PI3K pathway has been unclear. In this study, we used a single-vector lentiviral inducible shRNA system to selectively inactivate the three Class IA PI3Ks, PIK3CA, PIK3CB, and PIK3CD, to determine which PI3K isoforms are responsible for driving the abnormal proliferation of PTEN-deficient cancers. Down-regulation of PIK3CA in colorectal cancer cells harboring mutations in PIK3CA inhibited downstream PI3K signaling and cell growth. Surprisingly, PIK3CA depletion affected neither PI3K signaling nor cell growth in 3 PTEN-deficient cancer cell lines. In contrast, down-regulation of the PIK3CB isoform, which encodes p110beta, resulted in pathway inactivation and subsequent inhibition of growth in both cell-based and in vivo settings. This essential function of PIK3CB in PTEN-deficient cancer cells required its lipid kinase activity. Our findings demonstrate that although p110alpha activation is required to sustain the proliferation of established PIK3CA-mutant tumors, PTEN-deficient tumors are dependent instead on p110beta signaling. This unexpected finding demonstrates the need to tailor therapeutic approaches to the genetic basis of PI3K pathway activation to achieve optimal treatment response.
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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.