mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt.
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Summary
The data suggest that feedback down-regulation of receptor tyrosine kinase signaling is a frequent event in tumor cells with constitutive mTOR activation, and reversal of this feedback loop by rapamycin may attenuate its therapeutic effects, whereas combination therapy that ablates mTOR function and prevents Akt activation may have improved antitumor activity.
- Type
- article
- Published
- 2006-02-01
- Cited by
- 2,601
- References
- 28
- Access
- Open access
- OpenAlex
- https://openalex.org/W2126783165
- Semantic Scholar
- https://api.semanticscholar.org/CorpusID:2903877
Keywords
PI3K/AKT/mTOR pathway, Protein kinase B, Receptor tyrosine kinase, Cancer research, Insulin receptor
References
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- A new immunohistochemical antibody for the assessment of estrogen receptor status on routine formalin-fixed tissue samples.
- The PIK3CA gene is mutated with high frequency in human breast cancers
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- Will mTOR inhibitors make it as cancer drugs?
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- Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies.
- Insulin-induced insulin receptor substrate-1 degradation is mediated by the proteasome degradation pathway.
- Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition.
- Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR
- Addiction to Oncogenes--the Achilles Heal of Cancer
- Type 1 Insulin-like Growth Factor Receptor (IGF-IR) Signaling Inhibits Apoptosis Signal-regulating Kinase 1 (ASK1)*
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- The TSC1-2 tumor suppressor controls insulin–PI3K signaling via regulation of IRS proteins
Cited by
- Inhibidors de cinases com a estratègia terapèutica en neoplàsies limfoides
- Oleanolic acid but not ursolic acid induces cell death in HepG2 cells under starvation-induced autophagy
- Primary resistance to ATP-competitive mTOR inhibitors for the treatment of solid tumors
- IRS-1: auditing the effectiveness of mTOR inhibitors.
- AKT and cancer--is it all mTOR?
- Phosphorylated mTOR expression correlates with poor outcome in early-stage triple negative breast carcinomas.
- Phase I study of everolimus in pediatric patients with refractory solid tumors.
- Predicting drug susceptibility of non-small cell lung cancers based on genetic lesions.
- Molecular predictors of response to trastuzumab and lapatinib in breast cancer
- Personalized medicine in oncology: the future is now
- Phase II Trial of Gefitinib and Everolimus in Advanced Non-small Cell Lung Cancer
- From man to mouse and back again: advances in defining tumor AKTivities in vivo
- Targeted therapy for human epidermal growth factor receptor 2-positive breast cancer: can there be too many active drugs?
- Multiple signal pathways in obesity‐associated cancer
- Signalling Pathways Passing Src in Pancreatic Endocrine Tumours: Relevance for Possible Combined Targeted Therapies
- Acquired Resistance to Tamoxifen Is Associated with Loss of the Type I Insulin-like Growth Factor Receptor: Implications for Breast Cancer Treatment
- BRAFV600E Negatively Regulates the AKT Pathway in Melanoma Cell Lines
- Ophiopogonin B-induced autophagy in non-small cell lung cancer cells via inhibition of the PI3K/Akt signaling pathway
- Molecular characterization of anastrozole resistance in breast cancer: Pivotal role of the Akt/mTOR pathway in the emergence of de novo or acquired resistance and importance of combining the allosteric Akt inhibitor MK‐2206 with an aromatase inhibitor
- Integration of Different “-omics” Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells
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