DNA-damaging agents in cancer chemotherapy: serendipity and chemical biology

Chem Biol. 2013 May 23;20(5):648-59. doi: 10.1016/j.chembiol.2013.04.007.

Abstract

DNA-damaging agents have a long history of use in cancer chemotherapy. The full extent of their cellular mechanisms, which is essential to balance efficacy and toxicity, is often unclear. In addition, the use of many anticancer drugs is limited by dose-limiting toxicities as well as the development of drug resistance. Novel anticancer compounds are continually being developed in the hopes of addressing these limitations; however, it is essential to be able to evaluate these compounds for their mechanisms of action. This review covers the current DNA-damaging agents used in the clinic, discusses their limitations, and describes the use of chemical genomics to uncover new information about the DNA damage response network and to evaluate novel DNA-damaging compounds.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • DNA / genetics*
  • DNA Damage / drug effects*
  • Drug Discovery / methods*
  • Genomics / methods*
  • Humans
  • Neoplasms / drug therapy*

Substances

  • Antineoplastic Agents
  • DNA