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Critical Reviews™ in Oncogenesis

Publicou 4 edições por ano

ISSN Imprimir: 0893-9675

ISSN On-line: 2162-6448

SJR: 0.395 SNIP: 0.322 CiteScore™:: 2.5 H-Index: 54

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Antitumoral Activity of Sorafenib in Hepatocellular Carcinoma: Effects on Cell Survival and Death Pathways, Cell Metabolism Reprogramming, and Nitrosative and Oxidative Stress

Volume 21, Edição 5-6, 2016, pp. 413-432
DOI: 10.1615/CritRevOncog.2017021302
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RESUMO

Sorafenib is an oral multikinase inhibitor approved for the treatment of hepatocellular carcinoma (HCC). Its antitumor activity is attributed to inhibition of tyrosine kinase receptors (VEGFR, PDGFR, c-kit) and intracellular serine/threonine kinases (Raf), which alter gene expression to promote apoptosis and downregulate survival and angiogenesis pathways. The beneficial properties of sorafenib have also been related to a reduction in liver fibrosis trough regulation of TGF-βR-related STAT3 signaling. Sorafenib plays a role in the regulation of mitochondrial function, ATP, and autophagy, a process leading to either survival or apoptotic cell death depending on its intensity and duration, by altering several cellular pathways such as mTOR, AMPK, activating endoplasmic reticulum stress responses, and deregulating miRNAs that modulate autophagy. Sorafenib reduces S-nitrosation of cell death receptors and caspase-3, triggering a switch to caspase-3 from caspase-8. In this paper, we review the antitumor effects of sorafenib by interaction with cell survival and apoptosis pathways, metabolic reprogramming, and effect on oxidative and nitrosative stress, along with different mechanisms that might be involved in resistance to the drug.

CITADO POR
  1. Cole Daniel W., Svider Peter F., Shenouda Kerolos G., Lee Paul B., Yoo Nicholas G., McLeod Thomas M., Mutchnick Sean A., Yoo George H., Kaufman Randal J., Callaghan Michael U., Fribley Andrew M., Targeting the unfolded protein response in head and neck and oral cavity cancers, Experimental Cell Research, 382, 1, 2019. Crossref

  2. Yunus Madiha, Jansson Patric J., Kovacevic Zaklina, Kalinowski Danuta S., Richardson Des R., Tumor-induced neoangiogenesis and receptor tyrosine kinases – Mechanisms and strategies for acquired resistance, Biochimica et Biophysica Acta (BBA) - General Subjects, 1863, 7, 2019. Crossref

  3. Contreras Laura, Rodríguez-Gil Alfonso, Muntané Jordi, de la Cruz Jesús, Broad Transcriptomic Impact of Sorafenib and Its Relation to the Antitumoral Properties in Liver Cancer Cells, Cancers, 14, 5, 2022. Crossref

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