title: Adenoviral vectors for prodrug activation-based gene therapy for cancer.
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.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Doloff
authors.affiliation: Department of Cell and Molecular, Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USA. djw@bu.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Waxman
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D024201:Bystander Effect; D004261:DNA Replication; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000378:metabolism; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics* / Q000276:immunology; D011355:Prodrugs / Q000378:metabolism / Q000627:therapeutic use*; D011401:Promoter Regions, Genetic; D014779:Virus Replication
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs