MDA-7/IL-24 regulates proliferation, invasion and tumor cell radiosensitivity: a new cancer therapy?
The novel cytokine MDA-7/IL-24 was identified by subtractive hybridization in the mid-1990s as a cytokine 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 to non-transformed cells. Multiple studies from several laboratories have subsequently demonstrated that expression of IL-24 in tumor cells, but not in non-transformed cells, causes their growth arrest and ultimately cell death. In addition, IL-24 has been noted to be a radiosensitizing cytokine, which in part is due to the generation of reactive oxygen species (ROS) and causing endoplasmic reticulum stress. Recent publications of Phase I trial data have shown that a recombinant adenovirus to express MDA-7/IL-24 (Ad.mda-7 (INGN 241)) was safe and had tumoricidal effects in patients, which argues that IL-24 may have therapeutic value. This review describes what is known about the impact of IL-24 on tumor cell biology in addition to approaches that may enhance the toxicity of this novel cytokine.
Dent
Paul
P
Department of Biochemistry, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA. pdent@hsc.vcu.edu
Yacoub
Adly
A
Grant
Steven
S
Curiel
David T
DT
Fisher
Paul B
PB
D000818:Animals; D049109:Cell Proliferation; D016147:Genes, Tumor Suppressor; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D011836:Radiation Tolerance; D015398:Signal Transduction; D000099180:Interleukin-24
D007378:Interleukins; D000099180:Interleukin-24