Effect of DNA Repair Deficiencies on the Cytotoxicity of Drugs Used in Cancer Therapy - A Review
Jose Manuel Calderon-Montano,
Manuel Luis Orta,
Tumor cells often have defects in DNA repair pathways that make them vulnerable to specific DNA-damaging
anticancer agents. The identification of DNA repair defects in tumor cells and the evaluation of their influence on the cytotoxicity
of anticancer drugs are active areas of scientific investigation that may help rationalize and improve cancer chemotherapy.
This article reviews the available data on the influence of defects in proteins involved in the major DNA repair
pathways (i.e., homologous recombination, non-homologous end joining, base excision repair, nucleotide excision repair,
mismatch repair, Fanconi anemia repair, translesion synthesis and direct reversal repair) on the cytotoxicity of the FDAapproved
anticancer drugs. It is shown that specific deficiencies in these DNA repair pathways alter the cytotoxicity of 60
anticancer drugs, including classical DNA-targeting drugs (e.g., alkylating agents, cytotoxic antibiotics, DNA topoisomerase
inhibitors and antimetabolites) and other drugs whose primary pharmacological target is not the DNA (e.g., antimitotic
agents, hormonal and targeted therapies). This information may help predict response to anticancer drugs in patients
with tumors having specific DNA repair defects.
Keywords: Anticancer, chemotherapy, DNA damage, DNA damage response.
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