Targeting DNA-PK

This chapter explores the multifaceted roles of DNA-PK with particular focus on its functions in non-homologous end-joining (NHEJ) DNA repair. DNA-PK is the primary orchestrator of NHEJ but also regulates other biologic processes. The growing understanding of varied DNA-PK biologic roles highlights new avenues for cancer treatment. However, these multiple roles also imply challenges, particularly in combination therapies, with perhaps a higher risk of clinical toxicities than was previously envisioned. These considerations underscore the need for compelling and innovative strategies to accomplish effective clinical translation.