ArticleCancer cell2012
Inhibition of PI3K/mTOR leads to adaptive resistance in matrix-attached cancer cells.
Article in Cancer cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 249 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
249 citing papers in PubMed, 394 citations in OpenAlex.
- Safety lead-in of the MEK inhibitor trametinib in combination with GSK2141795, an AKT inhibitor, in patients with recurrent endometrial cancer: An NRG Oncology/GOG study.Gynecologic oncology · 2019Trial
- Targeting the PI3K/Akt Signaling Pathway: A Promising Therapeutic Strategy to Reduce Cancer Mortality and Overcome Chemoresistance.Health science reports · 2026Article
- mTORC1 activity suppresses ferroptosis through a SCARB1-dependent HDL-tocopherol uptake pathway.Molecular cell · 2026Article
- The Role of Neutrophil Extracellular Traps (NETs) in the Pathogenesis of Ovarian Cancer: New Insight and Future Perspectives.Molecular biotechnology · 2026Review
- Harnessing transcriptomics for discovery of natural products to overcome acquired cancer resistance.Archives of pharmacal research · 2026Review
- Metformin Sensitizes PTEN-deficient Prostate Cancer to PARP Inhibitors by Rebuilding NADPInternational journal of biological sciences · 2026Article
- NETs in ovarian cancer progression: innovative nanoparticle-based therapeutic strategies.European journal of medical research · 2025Review
- The anticancer effect of the HDAC inhibitor belinostat is enhanced by inhibitors of Bcl-xMolecular oncology · 2025Article
- Ferroptosis-related differential gene expression and immune correlates in luminal a subtype breast cancer: a prognostic model approach.World journal of surgical oncology · 2025Article
- O-GlcNAcylation of UBAP2L regulates stress granule formation and sunitinib resistance in clear cell renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- MLKL PARylation in the endothelial niche triggers angiocrine necroptosis to evade cancer immunosurveillance and chemotherapy.Nature cell biology · 2025Article
- eIF4A controls translation of estrogen receptor alpha and is a therapeutic target in advanced breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dual Inhibition of CDK4/6 and mTORC1 Establishes a Preclinical Strategy for Translocation Renal Cell Carcinoma.bioRxiv : the preprint server for biology · 2025Article
- BCL2 drives castration resistance in castration-sensitive prostate cancer by orchestrating reciprocal crosstalk between oncogenic pathways.Cell reports · 2025Article
- Organs on chips: fundamentals, bioengineering and applications.Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs · 2025Review
- Targeting Signaling Excitability in Cervical and Pancreatic Cancer Cells Through Combined Inhibition of FAK and PI3K.International journal of molecular sciences · 2025Article
- A multiplex single-cell RNA-Seq pharmacotranscriptomics pipeline for drug discovery.Nature chemical biology · 2025Article
- A thermoplastic chip for 2D and 3D correlative assays combining screening and high-resolution imaging of immune cell responses.Cell reports methods · 2025Article
- Emerging opportunities to treat drug-resistant breast cancer: Discovery of novel small-molecule inhibitors against different targets.Frontiers in pharmacology · 2025Review
- UBA1 inhibition sensitizes cancer cells to PARP inhibitors.Cell reports. Medicine · 2024Article
189 more citing papers are in PubMed but not listed here.
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 1 country.
Funding
Abstract
The PI3K/mTOR-pathway is the most commonly dysregulated pathway in epithelial cancers and represents an important target for cancer therapeutics. Here, we show that dual inhibition of PI3K/mTOR in ovarian cancer-spheroids leads to death of inner matrix-deprived cells, whereas matrix-attached cells are resistant. This matrix-associated resistance is mediated by drug-induced upregulation of cellular survival programs that involve both FOXO-regulated transcription and cap-independent translation. Inhibition of any one of several upregulated proteins, including Bcl-2, EGFR, or IGF1R, abrogates resistance to PI3K/mTOR inhibition. These results demonstrate that acute adaptive responses to PI3K/mTOR inhibition in matrix-attached cells resemble well-conserved stress responses to nutrient and growth factor deprivation. Bypass of this resistance mechanism through rational design of drug combinations could significantly enhance PI3K-targeted drug efficacy.
Indexed as
Identifiers
What OpenQuestion holds
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.