ArticleCancer cell2011
AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity.
Article in Cancer cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05189171 (MicroOrganoSphere Drug Screen to Lead Care), which is not on this map. Cited by 590 papers, 1 of them a synthesis that pooled it.
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.
MicroOrganoSphere Drug Screen to Lead Care (MODEL) Precision Oncology Pilot Trial in Colorectal Cancer (CRC)
Who cites it
590 citing papers in PubMed, 1 synthesis or guideline pooled it, 953 citations in OpenAlex.
- Effect of AKT1 (p. E17K) Hotspot Mutation on Malignant Tumorigenesis and Prognosis.Frontiers in cell and developmental biology · 2020Pooled it
- A phase 2 study of MK-2206 in patients with incurable adenoid cystic carcinoma (Alliance A091104).Cancer · 2024Trial
- A Phase 1b/2 Study of Alpelisib in Combination with Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.Targeted oncology · 2023Trial
- A phase II study of sapanisertib (TAK-228) a mTORC1/2 inhibitor in rapalog-resistant advanced pancreatic neuroendocrine tumors (PNET): ECOG-ACRIN EA2161.Investigational new drugs · 2022Trial
- Phase I/II study of bevacizumab with BKM120, an oral PI3K inhibitor, in patients with refractory solid tumors (phase I) and relapsed/refractory glioblastoma (phase II).Journal of neuro-oncology · 2019Trial
- Oncogenic RAS as an adaptive signaling ecosystem: context-dependent vulnerabilities and resistance-informed therapeutic design.Experimental hematology & oncology · 2026Review
- PI3K signaling in breast cancer: therapeutic advances versus adaptive resistance.The Journal of clinical investigation · 2026Review
- Targeting the PI3K/Akt Signaling Pathway: A Promising Therapeutic Strategy to Reduce Cancer Mortality and Overcome Chemoresistance.Health science reports · 2026Article
- Review
- Dual Targeting of FGFR4 and PI3K-mTOR Suppresses Tumor-Associated Phenotypes in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2026Article
- Inhibition of SHP2 enhances the effects of selective receptor tyrosine kinase inhibitors in untreated preclinical models of RET-mutated thyroid cancer.Investigational new drugs · 2026Article
- Small-molecule RAS/RAF inhibitors target RAS-driven cancers via allosteric RAF disruption.Nature communications · 2026Article
- Discovery of Cyclic Peptides Targeting the BRAF Dimer Interface as Dual Inhibitors.ACS pharmacology & translational science · 2026Article
- Insulin receptor substrate 2 (IRS2) confers resistance to PI3K pathway inhibition in PIK3CA mutant breast cancer.The Journal of biological chemistry · 2026Article
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- Effect of PI3K-p110α Inhibitor Alpelisib in the Differentiation and Effector Functions of M-CSF and GM-CSF Macrophages.International journal of molecular sciences · 2026Article
- mTORC1 activity suppresses ferroptosis through a SCARB1-dependent HDL-tocopherol uptake pathway.Molecular cell · 2026Article
- The role of KDM5B in creating synthetic vulnerabilities in combination with radiotherapy in melanoma cells.Cell communication and signaling : CCS · 2026Article
- Insulin Resistance and Inflammation.International journal of molecular sciences · 2026Review
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
530 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 2 countries.
Funding
Abstract
Activation of the PI3K-AKT pathway in tumors is modulated by negative feedback, including mTORC1-mediated inhibition of upstream signaling. We now show that AKT inhibition induces the expression and phosphorylation of multiple receptor tyrosine kinases (RTKs). In a wide spectrum of tumor types, inhibition of AKT induces a conserved set of RTKs, including HER3, IGF-1R, and insulin receptor. This is in part due to mTORC1 inhibition and in part secondary to a FOXO-dependent activation of receptor expression. PI3K-AKT inhibitors relieve this feedback and activate RTK signaling; this may attenuate their antitumor activity. Consistent with this model, we find that, in tumors in which AKT suppresses HER3 expression, combined inhibition of AKT and HER kinase activity is more effective than either alone.
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.