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- W4309492351 abstract "Cancer is a dreadful disease with limited clinical success despite the availability of countless chemotherapeutic and molecularly targeted therapeutics in the armamentarium. Systemic toxicity due to nonselective actions, i.e. off-target effects of the anticancer drugs and multidrug resistance are the two major culprits. Newer approaches have shown promise in addressing these issues alongside greater efficacy due to localized effects. Gene-directed enzyme–prodrug therapy (GDEPT) is one such modality under the broader umbrella of suicide gene therapy. The approach involves preferably delivering a gene(s) encoding an enzyme (transgene) for activating a coadministered prodrug in the target cell, e.g. tumor cell, which is subsequently converted to its active/toxic form, thereby inhibiting crucial processes for cell survival. The end effect is cell killing due to localized generation of toxic moieties in the target cells. Various transgene/prodrug pairs have been discovered and used successfully in many solid tumors. Despite lower transduction/transfection efficiency, the extent of cell killing depends on the bystander effect. Numerous successful early-phase clinical trials are a testimony of these approaches. The modality has several limitations, mostly stemming from inefficient delivery of the transgene. The physicochemical properties of the prodrugs are crucial too. At times, the aberrant nature of the growing tumor poses site-specific delivery of the gene and the prodrug. Growing number of studies appearing in the literature and the clinical trials indicate the interest of the scientific community in the approach. The researchers are revisiting these once tried-and-tested approaches with fresh perspectives from both the chemistry and biology standpoints. Future will deliver the promise offered by these strategies." @default.
- W4309492351 created "2022-11-28" @default.
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- W4309492351 date "2022-11-18" @default.
- W4309492351 modified "2023-10-13" @default.
- W4309492351 title "Gene‐Directed Enzyme–Prodrug Therapy ( <scp>GDEPT</scp> ) as a Suicide Gene Therapy Modality for Cancer Treatment" @default.
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- W4309492351 doi "https://doi.org/10.1002/9783527827855.ch6" @default.
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