DNA and its associated processes as targets for cancer therapy

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Abstract
DNA is the molecular target for many anticancer drugs. Alkylating agents generally interact non-specifically with DNA: the more effective ones tend to crosslink DNA. Antitumour antibiotics tend to be more specific in their interactions with DNA and are most often associated with modest sequence selectivity and targeting protein–DNA complexes. Code-reading molecules target either the major or minor groove of DNA and can read 1–2 turns of the helix. Polyamides target the minor groove, and triplex-forming molecules target the major groove. The efficacy of the small molecules that react with DNA is more dependent on their effect on DNA structure than on their sequence selectivity. Secondary DNA structures, such as G-quadruplex structures, represent a new class of molecular targets for DNA-interactive compounds that might be useful for targeting telomeres and transcriptional control. There is good reason to expect DNA to be a clinically important target for many years to come. More selective and less toxic compounds are in preparation and strategies to use the newer agents that target molecular receptors, in combination with DNA-reactive drugs, will maintain interest in DNA as a molecular target.