Selectively replicating adenoviruses for oncolytic therapy

T. K L Yoon, Toshiaki Shichinohe, Sylvie Laquerre, Noriyuki Kasahara

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 tissuespecific 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.

Original languageEnglish (US)
Pages (from-to)85-107
Number of pages23
JournalCurrent Cancer Drug Targets
Volume1
Issue number2
StatePublished - 2001
Externally publishedYes

Fingerprint

Adenoviridae
Neoplasms
Viral Genes
Therapeutics
Clinical Trials
Cell Engineering
Tropism
Leucovorin
Life Cycle Stages
Fluorouracil
Genetic Therapy
Suicide
Cisplatin
Radiation
Neoplasm Metastasis
Technology
Drug Therapy
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Pharmaceutical Science

Cite this

Yoon, T. K. L., Shichinohe, T., Laquerre, S., & Kasahara, N. (2001). Selectively replicating adenoviruses for oncolytic therapy. Current Cancer Drug Targets, 1(2), 85-107.

Selectively replicating adenoviruses for oncolytic therapy. / Yoon, T. K L; Shichinohe, Toshiaki; Laquerre, Sylvie; Kasahara, Noriyuki.

In: Current Cancer Drug Targets, Vol. 1, No. 2, 2001, p. 85-107.

Research output: Contribution to journalArticle

Yoon, TKL, Shichinohe, T, Laquerre, S & Kasahara, N 2001, 'Selectively replicating adenoviruses for oncolytic therapy', Current Cancer Drug Targets, vol. 1, no. 2, pp. 85-107.
Yoon, T. K L ; Shichinohe, Toshiaki ; Laquerre, Sylvie ; Kasahara, Noriyuki. / Selectively replicating adenoviruses for oncolytic therapy. In: Current Cancer Drug Targets. 2001 ; Vol. 1, No. 2. pp. 85-107.
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