The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance.
Tumours with specific DNA repair defects can be completely dependent on back-up DNA repair pathways for their survival. This dependence can be exploited therapeutically to induce synthetic lethality in tumour cells. For instance, homologous recombination (HR)-deficient tumours can be effectively targeted by DNA double-strand break-inducing agents. However, not all HR-defective tumours respond equally well to this type of therapy. Tumour cells may acquire resistance by invoking biochemical mechanisms that reduce drug action or by acquiring additional alterations in DNA damage response pathways. A thorough understanding of these processes is important for predicting treatment response and for the development of novel treatment strategies that prevent the emergence of therapy-resistant tumours.
Division of Molecular Pathology and Cancer Systems Biology Center, The Netherlands Cancer Institute, Plesmanlaan 121, 1066                 CX                 Amsterdam, The Netherlands.
Peter
P
Bouwman
Jos
J
Jonkers
D000970:Antineoplastic Agents / Q000627:therapeutic use; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016158:Genes, p53 / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D015398:Signal Transduction
D000970:Antineoplastic Agents