Use of preclinical models to assess the therapeutic potential of new drug candidates for bladder cancer.

Abstract:

:The purpose of this review is to demonstrate a successful use of preclinical models of bladder cancer to confirm the therapeutic potential of new promising drug candidates. The bladder has long been thought to be an ideal target for investigating therapies. When developing a new antineoplastic pharmaceutical agent, the bladder should be considered for use as an experimental model demonstrating initial proof of concept that if successful can be later assessed in further cancer indications. Non-muscle-invasive bladder carcinoma can be removed by transurethral resection but these cancers tend to recur in most patients. Conventional treatments decrease the recurrence rate but are associated with side effects and frequent failures. Thus, there is an obvious need for the development of highly effective targeted therapies with limited side effects. Accordingly, a double-promoter vector was developed, expressing diphtheria toxin A (DTA) under control of two different regulatory promoter sequences, H19 and IGF2. This vector was then used to transfect and to eradicate tumor cells in bladder cancer models, effectively destroying tumor cells without affecting normal cells. Our studies demonstrate the potential efficacy of the therapeutic vector and should be a solid base for future clinical studies. These models illuminate the path for future investigations of new drug candidates for bladder cancer.

journal_name

Semin Oncol

journal_title

Seminars in oncology

authors

Amit D,Gofrit ON,Matouk I,Birman T,Hochberg A

doi

10.1053/j.seminoncol.2012.08.006

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

534-42

issue

5

eissn

0093-7754

issn

1532-8708

pii

S0093-7754(12)00155-8

journal_volume

39

pub_type

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