The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches
Abstract
INTRODUCTION: The RAS/RAF/MAP kinase-ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) (MAPK) and the PI3K/AKT/mammalian target of rapamycin (mTOR) (PI3K) pathways are frequently deregulated in human cancer as a result of genetic alterations in their components or upstream activation of cell-surface receptors. These signalling cascades are regulated by complex feedback and cross-talk mechanisms. AREAS COVERED: In this review the key components of the MAPK and AKT pathways and their molecular alterations are described. The complex interactions between these signalling cascades are also analysed. EXPERT OPINION: The observation that the MAPK and the PI3K pathways are often deregulated in human cancer makes the components of these signalling cascades interesting targets for therapeutic intervention. Recently, the presence of compensatory loops that activate one pathway following the blockade of the other signalling cascade has been demonstrated. Therefore, the blockade of both pathways with combinations of signalling inhibitors might result in a more efficient anti-tumor effect as compared with a single agent. In addition, the MAPK and PI3K pathways are activated by mutations that coexist or can be mutually exclusive. In this regard, a large-scale characterization of the cancer genome might offer personalized cancer genomic information, which may improve the anti-tumor efficacy of signalling inhibitors.
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Cites
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Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies
Bahar, M. E., Kim, H. J., & Kim, D. R. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01705-z · Cited by 888
Ras Conformational Ensembles, Allostery, and Signaling
Lu, S., Jang, H., Muratcioglu, S., Gursoy, A., Keskin, O., Nussinov, R., & Zhang, J. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00542 · Cited by 355
TSC1 controls macrophage polarization to prevent inflammatory disease
Zhu, L., Yang, T., Li, L., Sun, L., Hou, Y., Hu, X., Zhang, L., Tian, H., Zhao, Q., Peng, J., et al. (2014) · Nature Communications · doi:10.1038/ncomms5696 · Cited by 288
Mechanism-based cancer therapy: resistance to therapy, therapy for resistance
Ramos, P., & Bentires-Alj, M. (2015) · Oncogene · doi:10.1038/onc.2014.314 · Cited by 272
Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view
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Metadata
- Authors
- De Luca, A., Maiello, M. R., D'Alessio, A., Pergameno, M., & Normanno, N.
- Venue
- Expert Opinion on Therapeutic Targets
- Publisher
- Informa UK Limited
- Published
- 2012-03-23
- Volume
- 16
- Issue
- sup2
- Pages
- S17-S27
- ISSN
- 1472-8222 (ISSN-L)
- 1744-7631
- OpenAlex
- W2165708858
- Cited by
- 735
- References
- 18
- FWCI
- 21.84
- Type
- journal article
- Language
- en
- Open access
- closed
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- De Luca, A., Maiello, M. R., D'Alessio, A., Pergameno, M., & Normanno, N. (2012). The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opinion on Therapeutic Targets. https://doi.org/10.1517/14728222.2011.639361
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