Apart from surgical approaches, the treatment of
cancer remains largely underpinned by
radiotherapy and pharmacological agents that cause damage to cellular
DNA, which ultimately causes
cancer cell death.
DNA polymerases, which are involved in the repair of cellular DNA damage, are therefore potential targets for inhibitors for improving the efficacy of
cancer therapy. They can be divided, according to their main function, into two groups, namely replicative and nonreplicative
enzymes. At least 15 different
DNA polymerases, including their homologs, have been discovered to date, which vary considerably in processivity and fidelity. Many of the nonreplicative (specialized)
DNA polymerases replicate
DNA in an error-prone fashion, and they have been shown to participate in multiple DNA damage repair and tolerance pathways, which are often aberrant in
cancer cells. Alterations in DNA repair pathways involving
DNA polymerases have been linked with
cancer survival and with treatment response to
radiotherapy or to classes of cytotoxic drugs routinely used for
cancer treatment, particularly
cisplatin,
oxaliplatin,
etoposide, and
bleomycin. Indeed, there are extensive preclinical data to suggest that
DNA polymerase inhibition may prove to be a useful approach for increasing the effectiveness of
therapies in patients with
cancer. Furthermore, specialized
DNA polymerases warrant examination of their potential use as clinical
biomarkers to select for particular
cancer therapies, to individualize treatment for patients.