Limits...
Regorafenib: an evidence-based review of its potential in patients with advanced liver cancer.

Ravi S, Singal AK - Core Evid (2014)

Bottom Line: In spite of HCC surveillance with repeated imaging, about 50% of patients are diagnosed at an advanced stage and are not amenable to curative treatment options.Sorafenib, a multikinase inhibitor, remains the standard of care for advanced HCC.Regorafenib, another multikinase inhibitor, has demonstrated inhibition of a broader range of kinases, along with higher inhibition potential in preclinical models.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

ABSTRACT
Hepatocellular carcinoma (HCC) is the second-most common cause of cancer-related death in the world. In spite of HCC surveillance with repeated imaging, about 50% of patients are diagnosed at an advanced stage and are not amenable to curative treatment options. Sorafenib, a multikinase inhibitor, remains the standard of care for advanced HCC. Over the last 5 years, several other medications have been tested in Phase III trials. However, they have not shown any added benefit over sorafenib. Regorafenib, another multikinase inhibitor, has demonstrated inhibition of a broader range of kinases, along with higher inhibition potential in preclinical models. After its safety and pharmacological properties was studied in Phase I trials, a Phase II study evaluating the role of Regorafenib in patients with advanced HCC who progressed on sorafenib therapy demonstrated efficacy and a manageable safety profile. A Phase III trial is ongoing, and its result will help us better evaluate the role of Regorafenib in patients with advanced HCC.

No MeSH data available.


Related in: MedlinePlus

Pathways involved in the development of hepatocellular carcinoma.Note: Multikinase inhibitors sorafenib and Regorafenib activate growth receptors, oncogenes, and developmental Wnt pathway.Abbreviations: IGF, insulin-like growth factor; TGF, transforming growth factor; VEGF, vascular endothelial growth factor; EGF, epidermal growth factor; FGF, fibroblast growth factor; PTEN, phosphatase and tensin homologue.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4109634&req=5

f2-ce-9-081: Pathways involved in the development of hepatocellular carcinoma.Note: Multikinase inhibitors sorafenib and Regorafenib activate growth receptors, oncogenes, and developmental Wnt pathway.Abbreviations: IGF, insulin-like growth factor; TGF, transforming growth factor; VEGF, vascular endothelial growth factor; EGF, epidermal growth factor; FGF, fibroblast growth factor; PTEN, phosphatase and tensin homologue.

Mentions: Hepatocarcinogenesis is a complex multistep process involving several pathways with activation of growth factors and their receptors, such as vascular endothelial growth factor (VEGF),11,12 fibroblast growth factor (FGF), epidermal growth factor (EGF),13 and insulin like growth factor;14,15 such oncogenes as RAS with activation of Ras-mitogen-activated protein kinase and RAF oncogenes;16,17 such developmental pathways as Wnt/β-catenin and hedgehog pathways;16,18,19 and inactivation or dysregulation of various tumor-suppressor genes (Figure 2).


Regorafenib: an evidence-based review of its potential in patients with advanced liver cancer.

Ravi S, Singal AK - Core Evid (2014)

Pathways involved in the development of hepatocellular carcinoma.Note: Multikinase inhibitors sorafenib and Regorafenib activate growth receptors, oncogenes, and developmental Wnt pathway.Abbreviations: IGF, insulin-like growth factor; TGF, transforming growth factor; VEGF, vascular endothelial growth factor; EGF, epidermal growth factor; FGF, fibroblast growth factor; PTEN, phosphatase and tensin homologue.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109634&req=5

f2-ce-9-081: Pathways involved in the development of hepatocellular carcinoma.Note: Multikinase inhibitors sorafenib and Regorafenib activate growth receptors, oncogenes, and developmental Wnt pathway.Abbreviations: IGF, insulin-like growth factor; TGF, transforming growth factor; VEGF, vascular endothelial growth factor; EGF, epidermal growth factor; FGF, fibroblast growth factor; PTEN, phosphatase and tensin homologue.
Mentions: Hepatocarcinogenesis is a complex multistep process involving several pathways with activation of growth factors and their receptors, such as vascular endothelial growth factor (VEGF),11,12 fibroblast growth factor (FGF), epidermal growth factor (EGF),13 and insulin like growth factor;14,15 such oncogenes as RAS with activation of Ras-mitogen-activated protein kinase and RAF oncogenes;16,17 such developmental pathways as Wnt/β-catenin and hedgehog pathways;16,18,19 and inactivation or dysregulation of various tumor-suppressor genes (Figure 2).

Bottom Line: In spite of HCC surveillance with repeated imaging, about 50% of patients are diagnosed at an advanced stage and are not amenable to curative treatment options.Sorafenib, a multikinase inhibitor, remains the standard of care for advanced HCC.Regorafenib, another multikinase inhibitor, has demonstrated inhibition of a broader range of kinases, along with higher inhibition potential in preclinical models.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

ABSTRACT
Hepatocellular carcinoma (HCC) is the second-most common cause of cancer-related death in the world. In spite of HCC surveillance with repeated imaging, about 50% of patients are diagnosed at an advanced stage and are not amenable to curative treatment options. Sorafenib, a multikinase inhibitor, remains the standard of care for advanced HCC. Over the last 5 years, several other medications have been tested in Phase III trials. However, they have not shown any added benefit over sorafenib. Regorafenib, another multikinase inhibitor, has demonstrated inhibition of a broader range of kinases, along with higher inhibition potential in preclinical models. After its safety and pharmacological properties was studied in Phase I trials, a Phase II study evaluating the role of Regorafenib in patients with advanced HCC who progressed on sorafenib therapy demonstrated efficacy and a manageable safety profile. A Phase III trial is ongoing, and its result will help us better evaluate the role of Regorafenib in patients with advanced HCC.

No MeSH data available.


Related in: MedlinePlus