A.D.N.J. de Grey, S.E. Artandi, F.C. Campbell, I. Dokal, L.J. Fairbairn, G.J. Graham, C.A.B. Jahoda, A.C.G. Porter

Despite enormous effort, progress in reducing mortality from cancer remains modest. Can a true cancer "cure" ever be developed, given the vast versatility that tumours derive from their genomic instability? Here we consider the efficacy, feasibility, and avoidability of side-effects 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 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 gene-deletion type of approach is the only way truly to overcome the hypermutation that makes tumours 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 anti-cancer promise, it is not too soon to begin working actively towards such a therapy.

Keywords (Optional): 
replicative capacity
stem cells
gene targeting