Anticancer gene

Anticancer genes are genes that, when ectopically overexpressed, specifically destroy tumour cells without harming normal cells.[1] 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.[2]

Examples

The first anticancer gene to be isolated was Apoptin, a gene encoded by the chicken anaemia virus genome.[2] 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.[3] The adenovirus E4orf4 is a viral protein with tumour-selective cell killing capabilities.[4] HAMLET encodes the milk protein α-lactalbumin and is active against cancer cells only when complexed with oleic acid.[5] Mda-7 (also known as IL-24) encodes a secreted cytokine and belongs to the IL-10 gene family.[6] Noxa, is a BH3-only protein of the Bcl-2 family, has recently been discovered as a specific killer of breast cancer cells.[7] Parvovirus-H1 NS1 is another viral protein carrying tumour-selective apoptosis capabilities.[8] ORCTL3, a cation transporter, was recently discovered as a novel anti-cancer gene.[9] Par-4 encodes a protein that features a leucine zipper and mediates many diverse signals for apoptosis at its endogenous expression level.[10] TRAIL (TNF related apoptosis-inducing ligand) is a member of the TNF family of apoptosis-inducing ligands [11]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.

See also
  • Oncogene
  • Gene therapy for cancer
  • Tumour suppressor gene

References
  1. Grimm, Stefan; Noteborn, Mathieu (2010). "Anticancer genes: inducers of tumour-specific cell death signalling". Trends in Molecular Medicine. 16 (2): 88–96. doi:10.1016/j.molmed.2009.12.002. PMID 20138582.
  2. Danen-Van Oorschot AA, Fischer DF, Grimbergen JM, Klein B, Zhuang S, Falkenburg JH, Backendorf C, Quax PH, Van der Eb AJ, Noteborn MH (May 1997). "Apoptin induces apoptosis in human transformed and malignant cells but not in normal cells". Proc. Natl. Acad. Sci. U.S.A. 94 (11): 5843–7. doi:10.1073/pnas.94.11.5843. PMC 20868. PMID 9159162.
  3. Ghavami S, Asoodeh A, Klonisch T, Halayko AJ, Kadkhoda K, Kroczak TJ, Gibson SB, Booy EP, Naderi-Manesh H, Los M (June 2008). "Brevinin-2R(1) semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway". J. Cell. Mol. Med. 12 (3): 1005–22. doi:10.1111/j.1582-4934.2008.00129.x. PMC 4401144. PMID 18494941.
  4. Gingras MC, Champagne C, Roy M, Lavoie JN (January 2002). "Cytoplasmic death signal triggered by SRC-mediated phosphorylation of the adenovirus E4orf4 protein". Mol. Cell. Biol. 22 (1): 41–56. doi:10.1128/mcb.22.1.41-56.2002. PMC 134208. PMID 11739721.
  5. Svensson M, Håkansson A, Mossberg AK, Linse S, Svanborg C (April 2000). "Conversion of alpha-lactalbumin to a protein inducing apoptosis". Proc. Natl. Acad. Sci. U.S.A. 97 (8): 4221–6. doi:10.1073/pnas.97.8.4221. PMC 18203. PMID 10760289.
  6. Su ZZ, Madireddi MT, Lin JJ, Young CS, Kitada S, Reed JC, Goldstein NI, Fisher PB (November 1998). "The cancer growth suppressor gene mda-7 selectively induces apoptosis in human breast cancer cells and inhibits tumor growth in nude mice". Proc. Natl. Acad. Sci. U.S.A. 95 (24): 14400–5. doi:10.1073/pnas.95.24.14400. PMC 24385. PMID 9826712.
  7. Suzuki S, Nakasato M, Shibue T, Koshima I, Taniguchi T (April 2009). "Therapeutic potential of proapoptotic molecule Noxa in the selective elimination of tumor cells". Cancer Sci. 100 (4): 759–69. doi:10.1111/j.1349-7006.2009.01096.x. PMID 19298224.
  8. Encyclopædia Britannica
  9. Irshad S, Mahul-Mellier AL, Kassouf N, Lemarie A, Grimm S (June 2009). "Isolation of ORCTL3 in a novel genetic screen for tumor-specific apoptosis inducers". Cell Death Differ. 16 (6): 890–8. doi:10.1038/cdd.2009.21. PMC 2683172. PMID 19282870.
  10. El-Guendy N, Rangnekar VM (February 2003). "Apoptosis by Par-4 in cancer and neurodegenerative diseases". Exp. Cell Res. 283 (1): 51–66. doi:10.1016/s0014-4827(02)00016-2. PMID 12565819.
  11. Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A (August 1997). "Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors". Science. 277 (5327): 818–21. doi:10.1126/science.277.5327.818. PMID 9242611.
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