Total Deletion of in Vivo Telomere Elongation Capacity: An Ambitious but Possibly Ultimate Cure for All Age-Related Human Cancers

• Published in: Annals of the New York Academy of Sciences Vol. 1019; no. 1; pp. 147 - 170
• Main Authors: DE GREY, AUBREY D. N. J., CAMPBELL, F CHARLES, DOKAL, INDERJEET, FAIRBAIRN, LESLIE J., GRAHAM, GERRY J., JAHODA, COLIN A. B., PORTERG, ANDREW C. G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2004
• Subjects: ALT; Animals; Antineoplastic Agents - pharmacology; Bone Marrow Cells - pathology; cancer; Cellular Senescence; chemoresistance; Disease Progression; DNA - ultrastructure; Gene Deletion; gene targeting; Humans; Immune System; Mice; Mice, Knockout; Models, Biological; Mutation; Neoplasm Metastasis; Neoplasms - drug therapy; Neoplasms - pathology; stem cell therapy; Stem Cells - metabolism; telomerase; Telomerase - metabolism; Telomere - ultrastructure
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1196/annals.1297.026

: Despite enormous effort, progress in reducing mortality from cancer remains modest. Can a true cancer “cure” ever be developed, given the vast versatility that tumors derive from their genomic instability? Here we consider the efficacy, feasibility, and safety of a therapy that, unlike any available or in development, could never be escaped by spontaneous changes of gene expression: the total elimination from the body of all genetic potential for telomere elongation, combined with stem cell therapies administered about once a decade to maintain proliferative tissues despite this handicap. We term this therapy WILT, for whole‐body interdiction of lengthening of telomeres. We first argue that a whole‐body gene‐deletion approach, however bizarre it initially seems, is truly the only way to overcome the hypermutation that makes tumors so insidious. We then identify the key obstacles to developing such a therapy and conclude that, while some will probably be insurmountable for at least a decade, none is a clear‐cut showstopper. Hence, given the absence of alternatives with comparable anticancer promise, we advocate working toward such a therapy.