» Articles » PMID: 28454211

Targeting the Ras/Raf/MEK/ERK Pathway in Hepatocellular Carcinoma

Overview
Journal Oncol Lett
Specialty Oncology
Date 2017 Apr 30
PMID 28454211
Citations 94
Authors
Affiliations
Soon will be listed here.
Abstract

Although the biological basis of hepatocellular carcinoma (HCC) remains unclear, effective treatments and improvement of the survival rate remain worthwhile research goals. Abnormal protein signaling pathways contributing to uncontrolled cell proliferation, differentiation, survival and apoptosis are biomarkers of the carcinogenic process. Certain mutated components or overexpression of the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway are increasingly being studied in HCC carcinogenesis. The present review addresses the effect of the Ras/Raf/MEK/ERK signaling pathway on the pathogenesis of HCC, and provides an update on the preclinical and clinical development of various inhibitors targeting this core signaling pathway, which include various Ras inhibitors, Raf inhibitors and MEK inhibitors for HCC.

Citing Articles

Gene-knockdown Methods for Silencing Nuclear-localized Insulin Receptors in Lung Adenocarcinoma Cells: A Bioinformatics Approach.

Ren Q, Ma H, Wang L, Qin J, Tian M, Zhang W Curr Genomics. 2025; 26(1):24-35.

PMID: 39911279 PMC: 11793068. DOI: 10.2174/0113892029298721240627095839.


Combination of Gene Therapy and Chemotherapy in a New Targeted Hybrid Nanosystem to Hepatocellular Carcinoma.

Farinha D, Sarmento-Ribeiro A, Faneca H Int J Nanomedicine. 2024; 19:12505-12527.

PMID: 39606562 PMC: 11598603. DOI: 10.2147/IJN.S474665.


Simultaneous detection of dynamic calcium signaling and ERK activity in living cells.

Zhang L, Mo Y, Mo S, Xia M, Wei C Biophys Rep. 2024; 10(5):304-314.

PMID: 39539282 PMC: 11554583. DOI: 10.52601/bpr.2023.230038.


Nicotine-induced CHRNA5 activation modulates CES1 expression, impacting head and neck squamous cell carcinoma recurrence and metastasis via MEK/ERK pathway.

Feng C, Mao W, Yuan C, Dong P, Liu Y Cell Death Dis. 2024; 15(10):785.

PMID: 39472448 PMC: 11522702. DOI: 10.1038/s41419-024-07178-4.


Ashwagandha-Induced Programmed Cell Death in the Treatment of Breast Cancer.

Kolodziejska R, Tafelska-Kaczmarek A, Pawluk M, Sergot K, Pisarska L, Wozniak A Curr Issues Mol Biol. 2024; 46(7):7668-7685.

PMID: 39057095 PMC: 11275341. DOI: 10.3390/cimb46070454.


References
1.
ONeil B, Goff L, Kauh J, Strosberg J, Bekaii-Saab T, Lee R . Phase II study of the mitogen-activated protein kinase 1/2 inhibitor selumetinib in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2011; 29(17):2350-6. PMC: 3107750. DOI: 10.1200/JCO.2010.33.9432. View

2.
Dhar D, Naora H, Yamanoi A, Ono T, Kohno H, Otani H . Requisite role of VEGF receptors in angiogenesis of hepatocellular carcinoma: a comparison with angiopoietin/Tie pathway. Anticancer Res. 2002; 22(1A):379-86. View

3.
Gollob J, Wilhelm S, Carter C, Kelley S . Role of Raf kinase in cancer: therapeutic potential of targeting the Raf/MEK/ERK signal transduction pathway. Semin Oncol. 2006; 33(4):392-406. DOI: 10.1053/j.seminoncol.2006.04.002. View

4.
Saini K, Loi S, de Azambuja E, Metzger-Filho O, Saini M, Ignatiadis M . Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK pathways in the treatment of breast cancer. Cancer Treat Rev. 2013; 39(8):935-46. DOI: 10.1016/j.ctrv.2013.03.009. View

5.
Davies B, Logie A, McKay J, Martin P, Steele S, Jenkins R . AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in.... Mol Cancer Ther. 2007; 6(8):2209-19. DOI: 10.1158/1535-7163.MCT-07-0231. View