title: Chapter One---Cancer terminator viruses and approaches for enhancing therapeutic outcomes.
abstract: No single or combinatorial therapeutic approach has proven effective in decreasing morbidity or engendering a cure of metastatic cancer. In principle, conditionally replication-competent adenoviruses that induce tumor oncolysis through cancer-specific replication hold promise for cancer therapy. However, a single-agent approach may not be adequate to completely eradicate cancer in a patient because most cancers arise from abnormalities in multiple genetic and signal transduction pathways and targeting disseminated metastases is difficult to achieve. Based on these considerations, a novel class of cancer destroying adenoviruses have been produced, cancer terminator viruses (CTVs), in which cancer-specific replication is controlled by the progression-elevated gene-3 promoter and replicating viruses produce a second transgene encoding an apoptosis-inducing and immunomodulatory cytokine, either melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) or interferon-γ. This review focuses on these viruses and ways to improve their delivery systemically and enhance their therapeutic efficacy.
authors.affiliation: Department of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Swadesh K
authors.initials: SK
authors.lastname: Das
authors.forename: Siddik
authors.initials: S
authors.lastname: Sarkar
authors.forename: Rupesh
authors.initials: R
authors.lastname: Dash
authors.forename: Paul
authors.initials: P
authors.lastname: Dent
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Wang
authors.forename: Devanand
authors.initials: D
authors.lastname: Sarkar
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008495:Medical Oncology / Q000639:trends; D045423:Microbubbles; D008954:Models, Biological; D008957:Models, Genetic; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy* / Q000821:virology*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D019076:Transgenes; D000099180:Interleukin-24
chemical_list: D007371:Interferon-gamma; D007378:Interleukins; D000099180:Interleukin-24