Targeting Ras/Raf/MEK/ERK Pathways in Hepatocellular Carcinoma (HCC): New Therapeutic Strategies

Targeting Ras/Raf/MEK/ERK Pathways in Hepatocellular Carcinoma (HCC): New Therapeutic Strategies
reza khedri,^1,* reza abouali,² Mohammad Amin Dehghani,³ hossein bahrami moghaddam,⁴
1. Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2. Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3. Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
4. Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Introduction: There are many ongoing studies regarding Hepatocellular carcinoma (HCC) carcinogenesis associated with mutated components or overexpression of the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen activated protein kinase (MEK)/extracellular signal regulated kinase (ERK) signaling pathway. The HCC incidence and development are highly related to the Ras/Raf/MEK/extracellular signal regulated kinase (ERK) signaling pathway, according to reports
Methods: The corresponding published articles in English were search on a database of PubMed by keywords of HCC, Ras/Raf/MEK/ERK pathways, Ras/Raf/MEK/ERK pathway inhibitors, sorafenib-resistant, combination therapeutic, treatment.
Results: Based on preclinical and clinical findings, HCC can be developed by abnormal activation of Ras/Raf/MEK/ERK signaling pathway. The combination of Ras/Raf/MEK/ERK pathway inhibitors and other pathway inhibitors can eliminate some preclinical concerns, but further clinical research is required to confirm such conditions. The RAF kinases and the Ras/Raf /MEK/ERK cascade can be inhibited by Sorafenib in HCC cells. The sorafenib-resistant HCC to have identified The Ras/Raf/MEK/ERK cascade has been reportedly shown as central target for this drug in accordance with cellular studies. The Ras/Raf/MEK/ERK cascade is a target for sorafenib based on clinical studies on serum phosphorylated ERK in tumor explants and in circulating tumor cells from HCC patients.
Conclusion: Accordingly, the activation of the Ras/Raf/MEK/ERK signalling pathway is very important in HCC incidence and development. In addition, Ras/Raf/MEK/ERK pathway inhibitors can be an effective option for HCC treatment in the near future.
Keywords: HCC, Ras/Raf/MEK/ERK pathway inhibitors, sorafenib-resistant, combination therapeutic.