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Published on: January 7, 2019
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.
Abstract:
One hallmark of neoplasia is abnormal differentiation. Induction of differentiation, by chemical or biological methods, provides a possible therapeutic intervention. "Differentiation therapy" is well documented in several model systems. These include melanoma, in which treatment with interferon-beta and the protein kinase C activator mezerein induces irreversible growth arrest and terminal differentiation culminating in programmed cell death. Subtraction hybridization between terminally differentiated and untreated melanoma cells identified melanoma differentiation-associated gene-7 (mda-7), which is selectively induced during the process of melanoma terminal differentiation. Since its identification seven years ago, mda-7 has been the object of intense focus because of its unique biological properties. Firstly, mda-7 is a secreted protein having cytokine-like properties and belonging to the IL-10 cytokine family. Based on this consideration, mda-7 was renamed IL-24. Secondly if delivered by means of an adenoviral vector, mda-7 induces selective apoptosis in cancer cells of diverse origin, while sparing their normal cellular counterparts. As such, mda-7 has become a novel tool for cancer gene therapy and is currently undergoing phase II clinical trials to determine its clinical efficacy in patients. The present review examines the biological properties of mda-7 and the signaling pathways that contribute to its unique cancer-specific apoptosis-inducing properties.
Insights
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.
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