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mda-7 (IL-24): signaling and functional roles
Devanand Sarkar1, Zao-zhong Su, Irina V Lebedeva
1Department of Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Biotechniques
|October 25, 2002
Summary
Melanoma differentiation-associated gene-7 (mda-7), now IL-24, selectively induces cancer cell death. Adenoviral delivery of mda-7 offers a promising new avenue for cancer gene therapy, sparing normal cells.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Neoplasia is characterized by abnormal cellular differentiation.
- Differentiation therapy, inducing terminal differentiation, is a potential cancer treatment.
- Melanoma differentiation-associated gene-7 (mda-7) was identified in differentiating melanoma cells.
Purpose of the Study:
- To review the biological properties of mda-7 (IL-24).
- To examine the signaling pathways mediating mda-7's cancer-specific apoptosis.
- To highlight mda-7's potential in cancer gene therapy.
Main Methods:
- Subtraction hybridization to identify mda-7.
- Analysis of mda-7's biological properties as a secreted cytokine.
- Investigating adenoviral vector-mediated delivery of mda-7 for cancer treatment.
Main Results:
- mda-7, a secreted protein in the IL-10 family, was renamed IL-24.
- Adenoviral delivery of mda-7 induces selective apoptosis in various cancer cells.
- Normal cells are spared from mda-7-induced apoptosis.
Conclusions:
- mda-7 (IL-24) exhibits unique cancer-specific apoptosis-inducing properties.
- mda-7 represents a novel tool for cancer gene therapy.
- mda-7 is currently in phase II clinical trials for patient efficacy.