DNA Damage as a Therapeutic Strategy

Synopsis

DNA alkylation leads to mutations and cancer, so at first it might seem unusual to use this as a mechanism to treat cancers. The strategy is that DNA is not rapidly expanding in most cells but is in growing tumor cells. Many of the drugs used in cancer therapy are cross-linking agents, which can be particularly detrimental to the activity of DNA polymerases. Further, the only other options for treating cancer are usually surgery, radiation therapy, and possibly alternate drugs. DNA repair can work against therapy, and in some cases, drugs such as O ⁶-benzylguanine have been used to boost the action of alkylating agents. A finite level of DNA damage can occur at non-tumor sites, and this can explain the increased incidence of later tumors (10–20 years) in individuals who have been given chemotherapy.

Introduction

Although most of the focus of this section is on the detrimental effects of DNA damage due to the introduction of mutations (leading to cancer and other diseases),...