MDA-7/IL-24 as a cancer therapeutic: From bench to bedside

Paul Dent*, Adly Yacoub, Hossein A. Hamed, Margaret A. Park, Rupesh Dash, Sujit K. Bhutia, Devanand Sarkar, Pankaj Gupta, Luni Emdad, Irina V. Lebedeva, Moira Sauane, Zhao Zhong Su, Mohamed Rahmani, William C. Broaddus, Harold F. Young, MacIej Lesniak, Steven Grant, David T. Curiel, Paul B. Fisher

*Corresponding author for this work

Research output: Contribution to journalReview article

41 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)725-731
Number of pages7
JournalAnti-Cancer Drugs
Volume21
Issue number8
DOIs
StatePublished - Sep 2010

Keywords

  • apoptosis
  • autophagy
  • melanoma differentiation associated gene 7

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

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    Dent, P., Yacoub, A., Hamed, H. A., Park, M. A., Dash, R., Bhutia, S. K., Sarkar, D., Gupta, P., Emdad, L., Lebedeva, I. V., Sauane, M., Su, Z. Z., Rahmani, M., Broaddus, W. C., Young, H. F., Lesniak, M., Grant, S., Curiel, D. T., & Fisher, P. B. (2010). MDA-7/IL-24 as a cancer therapeutic: From bench to bedside. Anti-Cancer Drugs, 21(8), 725-731. https://doi.org/10.1097/CAD.0b013e32833cfbe1