Employing tumor hypoxia for oncolytic therapy in breast cancer Journal Article
| Authors: | Chun, Y. S; Adusumilli, P. S.; Fong, Y. |
| Article Title: | Employing tumor hypoxia for oncolytic therapy in breast cancer |
| Abstract: | Hypoxia is a common tumor condition associated with metastases, therapeutic resistance, and poor patient survival. Forty percent of breast cancers are hypoxic, with a median oxygen concentration of 3.9%, and a third of tumors have regions less than 0.3%. Normal breast tissue is reported to have oxygen concentrations greater than 9%. This tumor hypoxia in breast cancer confers resistance to conventional radiation therapy and chemotherapy, as well as making estrogen-receptor-positive tumors less sensitive to hormonal therapy. Novel treatment modalities are needed to target hypoxic tumor cells. Lower tumor oxygen levels compared with surrounding normal tissues may be utilized to target and enhance herpes oncolytic viral therapy in breast cancer. Attenuated oncolytic herpes simplex viruses offer a unique cancer treatment by specifically infecting, replicating within, and lysing tumor cells. They carry genetically engineered mutations to reduce their virulence and attenuate their ability to infect normal tissues. Studies have shown the safety and efficacy of oncolytic herpes simplex viruses in treating breast cancer both in humans and in preclinical models. The placement of essential viral genes under the control of a hypoxia-responsive enhancer, which is upregulated selectively in hypoxic tissue, represents a promising strategy to target oncolytic viruses precisely to hypoxic cancer cells. In this review we describe strategies to harness hypoxia as a trigger for oncolytic viral gene expression in breast cancer, thereby increasing the specificity of viral infection, replication, and cytotoxicity to hypoxic areas of tumor. Such a targeted approach will increase efficacy in the therapy of hypoxic tumors while achieving a reduction in total dose of viral therapy. © Springer Science + Business Media, Inc. 2006. |
| Keywords: | vasculotropin; cancer survival; unclassified drug; gene mutation; mutation; clinical trial; fatigue; cisplatin; advanced cancer; drug dose reduction; nonhuman; antineoplastic agent; protein function; metastasis; breast cancer; gene expression; erythropoietin; epidermal growth factor receptor 2; herpes simplex; antineoplastic activity; cytotoxicity; breast neoplasms; protein p53; genetic vectors; genetic engineering; uterine cervix cancer; tumor cell; neoplasm metastasis; gene therapy; simplexvirus; oncolytic viruses; oncolytic virotherapy; tamoxifen; mitomycin c; cell hypoxia; antivirus agent; upregulation; virus replication; estrogen receptor; progesterone receptor; drug treatment failure; hypoxemia; hypoxia inducible factor 1alpha; virus strain; herpes simplex virus; anoxia; protein inhibitor; hypoxia-inducible factor 1, alpha subunit; muscle cramp; tirapazamine; gene expression regulation, viral; tumor cell destruction; hypoxia inducible factor 1; ribonucleotide reductase; virus virulence; hypoxia responsive element; thioredoxin; viral gene therapy; selective estrogen receptor modulator; small molecule transport agent; oxygen concentration; rabies vaccine |
| Journal Title: | Journal of Mammary Gland Biology and Neoplasia |
| Volume: | 10 |
| Issue: | 4 |
| ISSN: | 1083-3021 |
| Publisher: | Springer Science + Business Media, LLC |
| Date Published: | 2005-10-01 |
| Start Page: | 311 |
| End Page: | 318 |
| Language: | English |
| DOI: | 10.1007/s10911-006-9004-6 |
| PUBMED: | 16826462 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 24 October 2012" - "CODEN: JMBNF" - "Source: Scopus" |
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