Emerging cancer therapeutic opportunities target DNA-repair systems

Trends Pharmacol Sci. 2006 Jun;27(6):338-44. doi: 10.1016/j.tips.2006.04.007. Epub 2006 May 11.

Abstract

DNA-damaging agents have a central role in non-surgical cancer treatment. The balance between DNA damage and repair determines the final therapeutic consequences. An elevated DNA-repair capacity in tumor cells leads to drug or radiation resistance and severely limits the efficacy of these agents. Interference with DNA repair has emerged as an important approach in combination therapy against cancer. Anticancer targets in DNA-repair systems have emerged, against which several small-molecule compounds are currently undergoing clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / metabolism
  • DNA Damage*
  • DNA Repair / drug effects*
  • DNA, Neoplasm / drug effects*
  • DNA, Neoplasm / metabolism
  • DNA-Binding Proteins / metabolism
  • Drug Resistance, Neoplasm
  • Guanine / analogs & derivatives
  • Guanine / pharmacology
  • Guanine / therapeutic use
  • Humans
  • Morpholines / pharmacology
  • Morpholines / therapeutic use
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • O(6)-Methylguanine-DNA Methyltransferase / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Pyrones / pharmacology
  • Pyrones / therapeutic use
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use
  • Signal Transduction
  • Tumor Suppressor Proteins / metabolism

Substances

  • 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one
  • Antineoplastic Agents
  • Cell Cycle Proteins
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Morpholines
  • NU 1025
  • Pyrones
  • Quinazolines
  • Tumor Suppressor Proteins
  • O(6)-benzylguanine
  • Guanine
  • O(6)-Methylguanine-DNA Methyltransferase
  • Poly(ADP-ribose) Polymerases
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases