Liver-directed viral therapy for cancer p53-targeted adenoviruses and beyond.
Loss of p53 function is one of the most frequent genetic alterations in human cancers. Both replication-incompetent (rAd.p53, or SCH58500) and replication-selective (dl1520, or Onyx-015) adenoviruses are being developed for the treatment of p53-deficient cancers. Hepatic arterial infusion (HAI) has historically been used to selectively target colorectal tumors within the liver; consequently, regional therapy with adenovirus in this setting is an attractive approach. This article reviews Phase I and I/II HAI trial results with these adenovirus constructs.
Warren
Robert S
RS
Department of Surgery, University of California-San Francisco, 533 Parnassus Avenue, U-372, San Francisco, CA 94143-0790, USA. warrenr@surgery.ucsf.edu
Kirn
David H
DH
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D018014:Gene Transfer Techniques / Q000009:adverse effects / Q000639:trends; D016158:Genes, p53 / Q000235:genetics*; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods* / Q000639:trends; D005822:Genetic Vectors / Q000627:therapeutic use*; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D020714:Maximum Tolerated Dose; D014765:Viral Vaccines / Q000493:pharmacokinetics / Q000627:therapeutic use*
D014765:Viral Vaccines; C464532:dl1520