Total deletion of in vivo telomere elongation capacity: an ambitious but possibly ultimate cure for all age-related human cancers

Ann N Y Acad Sci. 2004 Jun;1019:147-70. doi: 10.1196/annals.1297.026.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Bone Marrow Cells / pathology
  • Cellular Senescence
  • DNA / ultrastructure
  • Disease Progression
  • Gene Deletion
  • Humans
  • Immune System
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Mutation
  • Neoplasm Metastasis
  • Neoplasms / drug therapy*
  • Neoplasms / pathology*
  • Stem Cells / metabolism
  • Telomerase / metabolism
  • Telomere / ultrastructure*

Substances

  • Antineoplastic Agents
  • DNA
  • Telomerase