DNA Damage Proteins and Response to Therapy in Head and Neck Cancer

Abstract

DNA-damaging agents such as cisplatin and radiotherapy have provided a cornerstone of treatment for squamous cell cancers of the head and neck (SCCHN). Cells possess multiple mechanisms for repairing different classes of DNA damage, including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), resolution of intrastrand cross-linking by the Fanconi anemia (FA) proteins, nonhomologous end joining (NHEJ), and homologous recombination (HR). Preclinical and a limited degree of clinical research has focused on evaluating whether changes in expression, mutation, or polymorphic variants in the many enzymes involved in these DNA repair pathways are involved in treatment resistance in SCCHN. This chapter will first summarize the proteins functioning in the complementary DNA-damage response pathways, then focus on the current data regarding their prognostic value in the clinic, noting the limitations of current retrospective evaluations, and discussing implications for future research.