Cancer is the second cause of death worldwide, surpassed only by cardiovascular diseases, due to the lack of early diagnosis, and high relapse rate after conventional therapies. Chemotherapy inhibits the rapid growth of cancer cells, but it also affects normal cells with fast proliferation rate. Therefore, it is imperative to develop other safe and more effective treatment strategies, such as gene therapy, in order to significantly improve the survival rate and life expectancy of patients with cancer. The aim of gene therapy is to transfect a therapeutic gene into the host cells to express itself and cause a beneficial biological effect. However, the efficacy of the proposed strategies has been insufficient for delivering the full potential of gene therapy in the clinic. The type of delivery vehicle (viral or non viral) chosen depends on the desired specificity of the gene therapy. The first gene therapy trials were performed with therapeutic genes driven by viral promoters such as the CMV promoter, which induces non-specific toxicity in normal cells and tissues, in addition to cancer cells. The use of tumor-specific promoters over-expressed in the tumor, induces specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several cancer- and/or tumor-specific promoters systems have been developed to target cancer cells. This review aims to provide up-to-date information concerning targeting gene therapy with cancer- and/or tumor-specific promoters including cancer suppressor genes, suicide genes, anti-tumor angiogenesis, gene silencing, and gene-editing technology, as well as the type of delivery vehicle employed. Gene therapy can be used to complement traditional therapies to provide more effective treatments.

The binding of ␣/␤-type small, acid-soluble spore proteins (SASP) to DNA of spores of Bacillus species is the major determinant of DNA resistance to a variety of damaging treatments. The primary sequence of ␣/␤-type SASP is highly conserved; however, the N-terminal third of these proteins is less well conserved than the C-terminal two-thirds. To determine the functional importance of residues in the N-terminal region of ␣/␤-type SASP, variants of SspC (a minor ␣/␤-type SASP from Bacillus subtilis) with modified N termini were generated and their structural and DNA binding properties studied in vitro and in vivo. SspC variants with deletions of up to 14 residues (ϳ20% of SspC residues) were able to bind DNA in vitro and adopted similar conformations when bound to DNA, as determined by circular dichroism spectroscopy and protein-protein cross-linking. Progressive deletion of up to 11 N-terminal residues resulted in proteins with progressively lower DNA binding affinity. However, SspC ⌬14 (in which 14 N-terminal residues have been deleted) showed significantly higher affinity for DNA than the larger proteins, SspC ⌬10 and SspC ⌬11 . The affinity of these proteins for DNA was shown to be largely dependent upon the charge of the first few N-terminal residues. These results are interpreted in the context of a model for DNA-dependent ␣/␤-type SASP protein-protein interaction involving the N-terminal regions of these proteins.

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