Selectively Replicating Adenoviruses for Oncolytic Therapy

Authors: Yoon T-k.Laurent; Shichinohe T.; Laquerre S.; Kasahara N.

Source: Current Cancer Drug Targets, Volume 1, Number 2, August 2001 , pp. 85-107(22)

Publisher: Bentham Science Publishers

Abstract:

The most prevalent problem in cancer therapy is the regrowth and metastasis of malignant cells after standard treatment with surgery, radiation, and / or chemotherapy. Gene therapy approaches have suffered from the inadequate transduction efficiencies of replication-defective vectors that have been used thus far. Replication-competent vectors, particularly adenoviruses that cause cytolysis as part of their natural life cycle, represent an emerging technology that shows considerable promise as a novel treatment option, particularly for locally advanced or recurrent cancer. A number of oncolytic adenoviruses that are designed to replicate selectively in tumor cells by targeting molecular lesions inherent in cancer, or by incorporation of tissue-specific promoters driving the early genes that initiate viral replication, are currently being tested in clinical trials. The results of these clinical trials indicate that, in its current form, oncolytic adenovirus therapy shows the best results and achieves an enhanced tumoricidal effect when used in combination with chemotherapeutic agents such as cisplatin, leucovorin and 5-fluorouracil. Nevertheless, each of the oncolytic adenoviruses in current use exhibits characteristic shortcomings, and there is still considerable room for improvement. Current strategies for improving the selectivity and efficacy of oncolytic adenoviruses include molecular engineering of tumor cell-specific binding tropism, selective modifications of viral early genes and incorporation of cellular promoters to achieve tumor-specific replication, augmentation of anti-tumor activity by incorporation of suicide genes, and manipulation of the immune response.

Keywords: Replicating Adenoviruses; Oncolytic Therapy; pro-apoptotic genes; endosomal compartment; histone acetyltransferase; E1A gene; xenograft models; immuno-costimulator 4-1BB

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1568009013334223

Publication date: 2001-08-01

• Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes, genes.
  Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cancer.
  As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

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