title: Total deletion of in vivo telomere elongation capacity: an ambitious but possibly ultimate cure for all age-related human cancers.
abstract: 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.
authors.affiliation: Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK. ag24@gen.cam.ac.uk
authors.forename: Aubrey D N J
authors.initials: AD
authors.lastname: de Grey
authors.forename: F Charles
authors.initials: FC
authors.lastname: Campbell
authors.forename: Inderjeet
authors.initials: I
authors.lastname: Dokal
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Fairbairn
authors.forename: Gerry J
authors.initials: GJ
authors.lastname: Graham
authors.forename: Colin A B
authors.initials: CA
authors.lastname: Jahoda
authors.forename: Andrew C G
authors.initials: AC
authors.lastname: Porterg
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000473:pathology; D016922:Cellular Senescence; D004247:DNA / Q000648:ultrastructure; D018450:Disease Progression; D017353:Gene Deletion; D006801:Humans; D007107:Immune System; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009154:Mutation; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D013234:Stem Cells / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000648:ultrastructure*
chemical_list: D000970:Antineoplastic Agents; D004247:DNA; D019098:Telomerase