The present invention concerns methods and compositions involving MDA-7 protein or an MDA-7-encoding nucleic acid in combination with either 1) a COX-2 selective inhibitor, such as celecoxib, 2) an Hsp90 inhibitor, such as geldanamycin, or a geldanamycin derivative or analog, 3) a vitamin E compound, for the treatment of cancer, 4) a TNF, such as TNF-alpha, 5) a VEGF inhibitor, or 6) an inhibitor of IL-10. In certain examples, a treatment for breast cancer is provided. In other examples a treatment for lung cancer is provided. Such examples involve, in some cases, an adenovirus vector that expresses MDA-7 protein.