Total deletion of in vivo telomere elongation capacity: an ambitious but possibly ultimate cure for all age-related human cancers.
Annals of the New York Academy of Sciences 2004 Jun 1; In press
de Grey A AD, Campbell F FC, Dokal I I, Fairbairn L LJ, Graham G GJ, Jahoda C CA, Porterg A AC
Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK. ag24@gen.cam.ac.uk
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.