WILT: an ambitious but truly un-escapable anti-cancer therapy
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
Department of Genetics, University of Cambridge, 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 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.
Key words:
cancer, replicative capacity, telomeres, stem cells, gene targeting, chemotherapy resistance
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