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- DNA and the chromosome – varied targets for chemotherapy

Numerous alterations in the nuclear environment occur in the development of cancer. In the past several decades, a major focus of cancer research has been discovering and understanding these tumourigenic events. These include small-scale changes in DNA sequences such as point mutations; larger scale chromosomal aberrations such as translocations, deletions, and amplifications; and other changes affecting chromatin structure including aberrant DNA methylation and histone modification. In all cases, these alterations can have dramatic direct effects on general nuclear activities, including DNA replication and repair, or on more specific activities such as the expression of key growth regulatory genes.

Coincident with understanding tumourigenesis has been the development of agents to treat patients with cancer. The current focus in anti-cancer drug design attempts to mimic the uniqueness of the cancer with appropriate therapy, in the expectation that treatment regimes will become increasingly specific for the cancer type and less deleterious to the overall health of the patient.

The goal of this review is to discuss some of the current strategies that specifically exploit our increasing knowledge of the nuclear environment in cancer cells to target specific cell classes for death. Anticancer drugs that target DNA have been used in the clinic, with varying degrees of success, for more than 40 years[1]. These compounds vary in the type of chemical interaction with DNA, the degree of sequence selectivity, the extent of lesion reversibility and/or ability to be repaired, and cancer cell susceptibility to their action. Classical DNA binding drugs have been considered as non-specific cytotoxic agents, with most of their therapeutic effects due to cytokinetic differences between normal and cancer cells. More recently, DNA interacting agents are being designed to affect specific nuclear functions, through interaction at designated primary DNA sequences, genomic locations, DNA secondary structures, or DNA-associated proteins[1].

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