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Annals of Surgical Oncology 10:596-605 (2003)
© 2003 Society of Surgical Oncology

NEW APPROACHES TO THE TREATMENT OF HEPATIC MALIGNANCIES

Viral Oncolysis for Malignant Liver Tumors

John T. Mullen, MD and Kenneth K. Tanabe, MD

From the Division of Surgical Oncology and Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Correspondence: Address correspondence and reprint requests to: Kenneth Tanabe, MD, Massachusetts General Hospital, 100 Blossom St., Cox Building 626, Boston, MA 02114; Fax: 617-724-3895.

ABSTRACT

Viral oncolysis represents a unique strategy to exploit the natural process of viral replication to kill tumor cells. Although this concept dates back nearly a century, recent advances in the fields of molecular biology and virology have enabled investigators to genetically engineer viruses with greater potency and tumor specificity. In this article we review the general mechanisms by which oncolytic viruses achieve their antineoplastic efficacy and specificity. We focus on the development of several classes of oncolytic viruses for the treatment of malignant liver tumors, including adenoviruses, vaccinia viruses, and herpes simplex viruses, and discuss the results of clinical trials for these viruses. We also describe results from our laboratory research program, which is focused on developing effective, liver tumor–specific Herpes simplex virus 1 mutants.

Key Words: Oncolysis • Replication-conditional viruses • Gene therapy • Clinical trials • Liver tumors




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