MDA-7/IL-24 as a cancer therapeutic: from bench to bedside.
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.
Dent
Paul
P
Department of Neurosurgery, Virginia Commonwealth University, Richmond, 23298-0035, USA. pdent@vcu.edu
Yacoub
Adly
A
Hamed
Hossein A
HA
Park
Margaret A
MA
Dash
Rupesh
R
Bhutia
Sujit K
SK
Sarkar
Devanand
D
Gupta
Pankaj
P
Emdad
Luni
L
Lebedeva
Irina V
IV
Sauane
Moira
M
Su
Zhao-Zhong
ZZ
Rahmani
Mohamed
M
Broaddus
William C
WC
Young
Harold F
HF
Lesniak
Maciej
M
Grant
Steven
S
Curiel
David T
DT
Fisher
Paul B
PB
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy; D006801:Humans; D007378:Interleukins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011836:Radiation Tolerance; D011877:Radionuclide Imaging; D015398:Signal Transduction; D000099180:Interleukin-24
D016207:Cytokines; D007378:Interleukins; D000099180:Interleukin-24