title: The DNA damage response: implications for tumor responses to radiation and chemotherapy.
abstract: Cellular responses to DNA damage are important determinants of both cancer development and cancer outcome following radiation therapy and chemotherapy. Identification of molecular pathways governing DNA damage signaling and DNA repair in response to different types of DNA lesions allows for a better understanding of the effects of radiation and chemotherapy on normal and tumor cells. Although dysregulation of the DNA damage response (DDR) is associated with predisposition to cancer development, it can also result in hypersensitivity or resistance of tumors to therapy and can be exploited for improvement of cancer treatment. We highlight the DDR pathways that are activated after treatment with radiation and different classes of chemotherapeutic drugs and describe mechanisms determining tumor sensitivity and resistance to these agents. Further, we discuss approaches to enhance tumor sensitivity to radiation and chemotherapy by modulating the DDR with a goal of enhancing the effectiveness of cancer therapies.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina 27710; email: michael.kastan@duke.edu , michael.goldstein@duke.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Goldstein
authors.forename: Michael B
authors.initials: MB
authors.lastname: Kastan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy; D011878:Radiotherapy
chemical_list: D000970:Antineoplastic Agents
keywords: DNA repair; cancer resistance; chemosensitization; radiosensitization; synthetic lethality