期刊
ANTI-CANCER DRUGS
卷 21, 期 8, 页码 725-731出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CAD.0b013e32833cfbe1
关键词
apoptosis; autophagy; melanoma differentiation associated gene 7
资金
- Samuel Waxman Cancer Research Foundation (SWCRF)
- National Foundation for Cancer Research (NFCR)
- [P01-CA104177]
- [R01-CA108325]
- [R01-DK52825]
- [R01-CA63753]
- [R01-CA77141]
- [R01-CA097318]
- [R01-CA098712]
- [P01-NS031492]
- NATIONAL CANCER INSTITUTE [R01CA127641, R01CA150214, R01CA108520, R01CA097318, P01CA104177, R01CA098712, R01CA141703, R01CA063753] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK052825] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P01NS031492] Funding Source: NIH RePORTER
The novel cytokine melanoma differentiation associated gene-7 (mda-7) was identified by subtractive hybridization in the mid-1990s as a protein whose expression increased during the induction of terminal differentiation, and that was either not expressed or was present at low levels in tumor cells compared with non-transformed cells. On the basis of conserved structure, chromosomal location and cytokine-like properties, MDA-7, has now been classified as a member of the expanding interleukin (IL)-10 gene family and designated as MDA-7/IL-24. Multiple studies have shown that the expression of MDA-7/IL-24 in a wide variety of tumor cell types, but not in the corresponding equivalent non-transformed cells, causes their growth arrest and ultimately cell death. In addition, MDA-7/IL-24 has been noted to be a radiosensitizing cytokine, which is partly because of the generation of reactive oxygen species and ceramide that cause endoplasmic reticulum stress. Phase I clinical trial data has shown that a recombinant adenovirus expressing MDA-7/IL-24 [Ad.mda-7 (INGN-241)] was safe and had measurable tumoricidal effects in over 40% of patients, which strongly argues that MDA-7/IL-24 may have significant therapeutic value. This review describes what is known about the impact of MDA-7/IL-24 on tumor cell biology and its potential therapeutic applications. Anti-Cancer Drugs 21: 725-731 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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