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Oncolytic virotherapy for advanced liver tumours.

Chang JF, Chen PJ, Sze DY, Reid T, Bartlett D, Kirn DH, Liu TC - J. Cell. Mol. Med. (2008)

Bottom Line: Despite decades of research, effective novel therapies for these cancers are urgently needed.This platform can also exploit the advantage of multiple intrinsic anti-cancer therapeutic mechanisms, combining direct viral oncolysis with therapeutic transgene expression.Recent advances in pre-clinical and clinical studies are revealing the potential of this unique therapeutic class, in particular for liver cancers.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Immunology, Washington University in Saint Louis, Saint Louis, MO, USA.

ABSTRACT
Primary and metastatic neoplasms of the liver account for more than a million deaths per year worldwide. Despite decades of research, effective novel therapies for these cancers are urgently needed. Oncolytic virotherapeutics represent a novel class of pharmacophore that holds promise for the treatment of hepatic neoplasms. Cancer-specific replication is followed by oncolysis, virus spreading and infection of adjacent cancer cells. This process is then repeated. Virotherapeutics target multiple genetic pathways involved in carcino-genesis, and demonstrate activity against apoptosis-resistant tumour cells. This platform can also exploit the advantage of multiple intrinsic anti-cancer therapeutic mechanisms, combining direct viral oncolysis with therapeutic transgene expression. Recent advances in pre-clinical and clinical studies are revealing the potential of this unique therapeutic class, in particular for liver cancers. This review summarizes the available data on applying oncolytic virotherapeutics to hepatic neoplasms to date, and discusses the challenges and future directions for virotherapy.

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Related in: MedlinePlus

Long-term inhibition of HBV replication in a representative HCC patient after treatment with oncolytic poxvirus JX-594.
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fig03: Long-term inhibition of HBV replication in a representative HCC patient after treatment with oncolytic poxvirus JX-594.

Mentions: In addition to the antitumoural effect, it will be crucial to determine what impact oncolytic virotherapy has on underlying hepatitis in HCC patients. Three HCC patients treated with oncolytic vaccinia virus JX-594 via IT injection were chronically infected with hepatitis B virus (HBV) and had been treated with antiviral medications prior to study enrolment. After JX-594 treatment, all three patients experienced sustained reduction in HBV genome levels, with decreases ranging from 51% to 90% (Fig. 3) [18]. Possible mechanisms include induction of antiviral cytokines, many of which have been known to have anti-HBV effects (e.g. TNF-α, IFN-γ) [18]. Whether this phenomenon is applicable to other HBV- or hepatitis C virus (HCV)-associated HCCs is yet to be determined. In addition, most patients with chronic HBV infection are also on chronic antiviral medications, and the impact of concurrent anti-hepatitis medications on oncolytic viruses needs to be studied. Testing virotherapeutics in HBV animal models [40] will also provide more insights.


Oncolytic virotherapy for advanced liver tumours.

Chang JF, Chen PJ, Sze DY, Reid T, Bartlett D, Kirn DH, Liu TC - J. Cell. Mol. Med. (2008)

Long-term inhibition of HBV replication in a representative HCC patient after treatment with oncolytic poxvirus JX-594.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4496138&req=5

fig03: Long-term inhibition of HBV replication in a representative HCC patient after treatment with oncolytic poxvirus JX-594.
Mentions: In addition to the antitumoural effect, it will be crucial to determine what impact oncolytic virotherapy has on underlying hepatitis in HCC patients. Three HCC patients treated with oncolytic vaccinia virus JX-594 via IT injection were chronically infected with hepatitis B virus (HBV) and had been treated with antiviral medications prior to study enrolment. After JX-594 treatment, all three patients experienced sustained reduction in HBV genome levels, with decreases ranging from 51% to 90% (Fig. 3) [18]. Possible mechanisms include induction of antiviral cytokines, many of which have been known to have anti-HBV effects (e.g. TNF-α, IFN-γ) [18]. Whether this phenomenon is applicable to other HBV- or hepatitis C virus (HCV)-associated HCCs is yet to be determined. In addition, most patients with chronic HBV infection are also on chronic antiviral medications, and the impact of concurrent anti-hepatitis medications on oncolytic viruses needs to be studied. Testing virotherapeutics in HBV animal models [40] will also provide more insights.

Bottom Line: Despite decades of research, effective novel therapies for these cancers are urgently needed.This platform can also exploit the advantage of multiple intrinsic anti-cancer therapeutic mechanisms, combining direct viral oncolysis with therapeutic transgene expression.Recent advances in pre-clinical and clinical studies are revealing the potential of this unique therapeutic class, in particular for liver cancers.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Immunology, Washington University in Saint Louis, Saint Louis, MO, USA.

ABSTRACT
Primary and metastatic neoplasms of the liver account for more than a million deaths per year worldwide. Despite decades of research, effective novel therapies for these cancers are urgently needed. Oncolytic virotherapeutics represent a novel class of pharmacophore that holds promise for the treatment of hepatic neoplasms. Cancer-specific replication is followed by oncolysis, virus spreading and infection of adjacent cancer cells. This process is then repeated. Virotherapeutics target multiple genetic pathways involved in carcino-genesis, and demonstrate activity against apoptosis-resistant tumour cells. This platform can also exploit the advantage of multiple intrinsic anti-cancer therapeutic mechanisms, combining direct viral oncolysis with therapeutic transgene expression. Recent advances in pre-clinical and clinical studies are revealing the potential of this unique therapeutic class, in particular for liver cancers. This review summarizes the available data on applying oncolytic virotherapeutics to hepatic neoplasms to date, and discusses the challenges and future directions for virotherapy.

Show MeSH
Related in: MedlinePlus