The DOI matches its Crossref record; 125 of the 125 references it cites were found in a registry or an index.
The Ras/MAPK pathway and hepatocarcinoma: pathogenesis and therapeutic implications
Abstract
Background: Hepatocellular carcinoma (HCC) is still a major health problem, often diagnosed at an advanced stage. The multikinase inhibitor sorafenib is to date the sole approved systemic therapy. Several signalling pathways are implicated in tumour development and progression. Among these pathways, the Ras/MAPK pathway is activated in 50–100% of human HCC s and is correlated with a poor prognosis. The aim of this work was to review the main intracellular mechanisms leading to aberrant Ras pathway activation in HCC and the potential therapeutic implications. Materials and methods: This review is based on the material found on PubMed up to December 2014. ‘Ras signaling, Ras dysregulation, Ras inhibition, MAPK pathway, cancer, hepatocarcinoma and liver cancer’ alone or in combination were the main terms used for online research. Results: Multiple mechanisms lead to the deregulation of the Ras pathway in liver cancer. Ras and Raf gene mutations are rare events in human hepatocarcinogenesis in contrast to experimental models in rodents. Downregulation of several Ras/MAPK pathway inhibitors such as GAP s, RASSF proteins, DUSP 1, Sprouty and Spred proteins is largely implicated in the aberrant activation of this pathway in the context of wild‐type Ras and Raf genes. Epigenetic or post‐transcriptional mechanisms lead to the downregulation of these tumour suppressor genes. Conclusion: Ras/MAPK pathway effectors may be considered as potential therapeutic targets in the field of HCC. In particular after the arrival of sorafenib, more Ras/MAPK inhibitors have emerged and are still in preclinical or clinical investigation for HCC therapy.
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Anstee, Q. M., Reeves, H. L., Kotsiliti, E., Govaere, O., & Heikenwalder, M. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0145-7 · Cited by 1,392
Hepatocellular carcinoma: signaling pathways and therapeutic advances
Zheng, J., Wang, S., Xia, L., Sun, Z., Chan, K. M., Bernards, R., Qin, W., Chen, J., Xia, Q., & Jin, H. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02075-w · Cited by 341
MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma
Moon, H., & Ro, S. W. (2021) · Cancers · doi:10.3390/cancers13123026 · Cited by 326
Current and Future Treatment of Hepatocellular Carcinoma: An Updated Comprehensive Review
Daher, S., Massarwa, M., Benson, A. A., & Khoury, T. (2018) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2017.00031 · Cited by 304
A novel prognostic index of hepatocellular carcinoma based on immunogenomic landscape analysis
Xiao, H., Wang, B., Xiong, H., Guan, J., Wang, J., Tan, T., Lin, K., Zou, S., Hu, Z., & Wang, K. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30015 · Cited by 43
Metadata
- Authors
- Delire, B., & Stärkel, P.
- Venue
- European Journal of Clinical Investigation
- Publisher
- Wiley
- Published
- 2015-05-11
- Volume
- 45
- Issue
- 6
- Pages
- 609-623
- ISSN
- 0014-2972 (ISSN-L)
- 1365-2362
- OpenAlex
- W1997769423
- Cited by
- 275
- References
- 125
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- closed
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