title: Melanoma differentiation associated gene-7 (mda-7)/IL-24: a 'magic bullet' for cancer therapy?
abstract: An ideal cancer gene therapy would selectively kill cancer cells without harming normal cells and induce multipronged 'bystander' antitumor effects, facilitating eradication of both primary and metastatic tumors. Melanoma differentiation associated gene-7 (mda-7)/interleukin-24 (IL-24) exhibits all of these attributes and more. It induces cancer-selective apoptosis, inhibits angiogenesis, stimulates an antitumor immune response, sensitizes cancer cells to radiation and other modalities of conventional therapies, and exhibits profound 'bystander' activity eliminating both primary and distant tumors in animal models. Moreover, a replication-incompetent adenovirus expressing mda-7/IL-24, Ad.mda-7 (INGN-241), has now undergone evaluation in a Phase I clinical trial for multiple solid tumors, including melanomas, and has demonstrated safety and significant objective clinical activity. Considering these exciting observations, mda-7/IL-24 is being hailed as a 'magic bullet' for cancer gene therapy. This review elaborates on the pleiotropic properties of mda-7/IL-24 and unravels novel aspects of the molecule mandating future studies and expanded clinical applications.
authors.affiliation: Columbia University Medical Center, Department of Urology, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA. ds2039@columbia.edu
authors.forename: Devanand
authors.initials: D
authors.lastname: Sarkar
authors.forename: Irina V
authors.initials: IV
authors.lastname: Lebedeva
authors.forename: Pankaj
authors.initials: P
authors.lastname: Gupta
authors.forename: Luni
authors.initials: L
authors.lastname: Emdad
authors.forename: Moira
authors.initials: M
authors.lastname: Sauane
authors.forename: Paul
authors.initials: P
authors.lastname: Dent
authors.forename: David T
authors.initials: DT
authors.lastname: Curiel
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D024201:Bystander Effect; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D008545:Melanoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control; D012878:Skin Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome; D000099180:Interleukin-24
chemical_list: D007378:Interleukins; D000099180:Interleukin-24