Anticancer genes are genes that, when ectopically overexpressed, specifically destroy tumour cells without harming normal cells. This cell destruction can be due to a variety of mechanisms, such as apoptosis, mitotic catastrophe followed by apoptosis or necrosis, and autophagy. Anticancer genes emerged from studies on cancer cells in the late 1990s.
The first anticancer gene to be isolated was Apoptin, a gene encoded by the chicken anaemia virus genome. Brevinin-2R is a short anti-microbial peptide of only 25 amino acids, a so-called non-hemolytic defensin, isolated from the skin of the frog species Rana ridibunda. The adenovirus E4orf4 is a viral protein with tumour-selective cell killing capabilities. HAMLET encodes the milk protein α-lactalbumin and is active against cancer cells only when complexed with oleic acid. Mda-7 (also known as IL-24) encodes a secreted cytokine and belongs to the IL-10 gene family. Noxa, is a BH3-only protein of the Bcl-2 family, has recently been discovered as a specific killer of breast cancer cells. Parvovirus-H1 NS1 is another viral protein carrying tumour-selective apoptosis capabilities. ORCTL3, a cation transporter, was recently discovered as a novel anti-cancer gene. Par-4 encodes a protein that features a leucine zipper and mediates many diverse signals for apoptosis at its endogenous expression level. TRAIL (TNF related apoptosis-inducing ligand) is a member of the TNF family of apoptosis-inducing ligands TP53 is another anti-cancer/anti-tumor gene (elephants have twenty copies of the TP53 gene).
Some of these genes are in clinical development. TRAIL, Mda-7, HAMLET are the clinically most advanced anticancer genes.
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