Other new targeted therapies

Jairo A. Garcia, Lewis Rowland Roberts

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

There are several novel potential molecules and pathways involved in the pathogenesis of hepatocellular carcinoma (HCC) against which targeted therapies are under development as new drugs for HCC treatment. Heparan sulfate proteoglycans are important mediators of cancer cell signaling. The heparin sulfate-mimetic agent PI-88 and newer derivatives as well as small-molecule inhibitors are being developed for specific targeting of the heparan sulfate-modifying enzymes heparanase and the heparin-degrading endosulfatases sulfatase 1 and sulfatase 2 in cancer. The ubiquitin-proteasome pathway plays a central role in cellular protein degradation, including aberrant degradation of tumor supressor proteins. Proteasome inhibitors, such as bortezomib, appear to target the proteasome in HCC through effects on Akt signaling. Dysregulation of apoptosis is a major phenotype of cancer. The TNF-related apoptosis-inducing ligand and X-linked inhibitor of apoptosis protein are key targets of strategies to induce apoptosis in cancer. The IGF pathway has been implicated in development of HCC. Monoclonal antibodies directed against the IGF-1 receptor are under evaluation for treatment of HCC. The heparan sulfate proteoglycan glypican 3 (GPC3) is one of the most highly expressed proteins in HCC. GPC3 is therefore a natural target for therapy of HCC. A humanized monoclonal antibody against GPC3 is in clinical trials for HCC treatment. Inhibitors of the oncogenic Hedgehog, Myc and Wnt/b-catenin signaling pathways are also in preclinical development and of potential use for treatment of HCC.

Original languageEnglish (US)
Title of host publicationTargeted Therapies for Hepatocellular Carcinoma
PublisherFuture Medicine Ltd.
Pages85-96
Number of pages12
ISBN (Print)9781780840628, 9781780841311
DOIs
StatePublished - Dec 1 2011

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Hepatocellular Carcinoma
Glypicans
Sulfatases
Heparan Sulfate Proteoglycans
Therapeutics
Proteasome Endopeptidase Complex
Neoplasms
Heparin
X-Linked Inhibitor of Apoptosis Protein
TNF-Related Apoptosis-Inducing Ligand
Apoptosis
Antibodies, Monoclonal, Humanized
Catenins
IGF Type 1 Receptor
Proteasome Inhibitors
Heparitin Sulfate
Ubiquitin
Proteolysis
Sulfates
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Garcia, J. A., & Roberts, L. R. (2011). Other new targeted therapies. In Targeted Therapies for Hepatocellular Carcinoma (pp. 85-96). Future Medicine Ltd.. https://doi.org/10.2217/EBO.11.267

Other new targeted therapies. / Garcia, Jairo A.; Roberts, Lewis Rowland.

Targeted Therapies for Hepatocellular Carcinoma. Future Medicine Ltd., 2011. p. 85-96.

Research output: Chapter in Book/Report/Conference proceedingChapter

Garcia, JA & Roberts, LR 2011, Other new targeted therapies. in Targeted Therapies for Hepatocellular Carcinoma. Future Medicine Ltd., pp. 85-96. https://doi.org/10.2217/EBO.11.267
Garcia JA, Roberts LR. Other new targeted therapies. In Targeted Therapies for Hepatocellular Carcinoma. Future Medicine Ltd. 2011. p. 85-96 https://doi.org/10.2217/EBO.11.267
Garcia, Jairo A. ; Roberts, Lewis Rowland. / Other new targeted therapies. Targeted Therapies for Hepatocellular Carcinoma. Future Medicine Ltd., 2011. pp. 85-96
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