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Hitting the bull's eye: novel directed cancer therapy through helicase-targeted synthetic lethality.

Abstract
Designing strategies for anti-cancer therapy have posed a significant challenge. One approach has been to inhibit specific DNA repair proteins and their respective pathways to enhance chemotherapy and radiation therapy used to treat cancer patients. Synthetic lethality represents an approach that exploits pre-existing DNA repair deficiencies in certain tumors to develop inhibitors of DNA repair pathways that compensate for the tumor-associated repair deficiency. Since helicases play critical roles in the DNA damage response and DNA repair, particularly in actively dividing and replicating cells, it is proposed that the identification and characterization of synthetic lethal relationships of DNA helicases will be of value in developing improved anti-cancer treatment strategies. In this review, we discuss this hypothesis and current evidence for synthetic lethal interactions of eukaryotic DNA helicases in model systems.
AuthorsMonika Aggarwal, Robert M Brosh Jr
JournalJournal of cellular biochemistry (J Cell Biochem) Vol. 106 Issue 5 Pg. 758-63 (Apr 01 2009) ISSN: 1097-4644 [Electronic] United States
PMID19173305 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Review)
Chemical References
  • Antineoplastic Agents
  • DNA Helicases
Topics
  • Antineoplastic Agents (pharmacology)
  • DNA Helicases (antagonists & inhibitors)
  • DNA Repair (drug effects)
  • Drug Delivery Systems
  • Drug Design
  • Humans

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