Abstract
Cancer cell heterogeneity is a common feature - both between patients diagnosed with the same cancer and within an individual patient’s tumor - and leads to widely different response rates to cancer therapies and the potential for the emergence of drug resistance. Diverse therapeutic approaches have been developed to combat the complexity of cancer, including individual treatment modalities designed to target tumor heterogeneity. This review discusses adenoviral vectors and how they can be modified to replicate in a cancer-specific manner and deliver therapeutic genes under multi-tiered regulation to target tumor heterogeneity, including heterogeneity associated with cancer stem cell-like subpopulations. Strategies that allow for combination of prodrug-activation gene therapy with a novel replication-conditional, heterogeneous tumor-targeting adenovirus are discussed, as are the benefits of using adenoviral vectors as tumor-targeting oncolytic vectors. While the anticancer activity of many adenoviral vectors has been well established in preclinical studies, only limited successes have been achieved in the clinic, indicating a need for further improvements in activity, specificity, tumor cell delivery and avoidance of immunogenicity.
Keywords: Cancer gene therapy, cytochrome P450 prodrug activation, replication-conditional adenovirus, oncolytic adenovirus, tumor heterogeneity.
Anti-Cancer Agents in Medicinal Chemistry
Title:Adenoviral Vectors for Prodrug Activation-based Gene Therapy for Cancer
Volume: 14 Issue: 1
Author(s): Joshua C. Doloff and David J. Waxman
Affiliation:
Keywords: Cancer gene therapy, cytochrome P450 prodrug activation, replication-conditional adenovirus, oncolytic adenovirus, tumor heterogeneity.
Abstract: Cancer cell heterogeneity is a common feature - both between patients diagnosed with the same cancer and within an individual patient’s tumor - and leads to widely different response rates to cancer therapies and the potential for the emergence of drug resistance. Diverse therapeutic approaches have been developed to combat the complexity of cancer, including individual treatment modalities designed to target tumor heterogeneity. This review discusses adenoviral vectors and how they can be modified to replicate in a cancer-specific manner and deliver therapeutic genes under multi-tiered regulation to target tumor heterogeneity, including heterogeneity associated with cancer stem cell-like subpopulations. Strategies that allow for combination of prodrug-activation gene therapy with a novel replication-conditional, heterogeneous tumor-targeting adenovirus are discussed, as are the benefits of using adenoviral vectors as tumor-targeting oncolytic vectors. While the anticancer activity of many adenoviral vectors has been well established in preclinical studies, only limited successes have been achieved in the clinic, indicating a need for further improvements in activity, specificity, tumor cell delivery and avoidance of immunogenicity.
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Cite this article as:
Doloff C. Joshua and Waxman J. David, Adenoviral Vectors for Prodrug Activation-based Gene Therapy for Cancer, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (1) . https://dx.doi.org/10.2174/18715206113139990309
DOI https://dx.doi.org/10.2174/18715206113139990309 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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