DNA damage response and breast cancer development: Possible therapeutic applications of ATR, ATM, PARP, BRCA1 inhibition

DNA Repair (Amst). 2021 Feb:98:103032. doi: 10.1016/j.dnarep.2020.103032. Epub 2020 Dec 17.

Abstract

Breast cancer is the most common and significant cancers in females regarding the loss of life quality. Similar to other cancers, one of the etiologic factors in breast cancer is DNA damage. A plethora of molecules are responsible for sensing DNA damage and mediating actions which lead to DNA repair, senescence, cell cycle arrest and if damage is unbearable to apoptosis. In each of these, aberrations leading to unrepaired damage was resulted in uncontrolled proliferation and cancer. Another cellular function is autophagy defined as a process eliminating of unnecessary proteins in stress cases involved in pathogenesis of cancer. Knowing their role in cancer, scholars have tried to develop strategies in order to target DDR and autophagy. Further, the interactions of DDR and autophagy plus their regulatory role on each other have been focused simultaneously. The present review study has aimed to illustrate the importance of DDR and autophagy in breast cancer according to the related studies and uncover the relation between DDR and autophagy and its significance in breast cancer therapy.

Keywords: ATG; Autophagy; Beclin-1; Breast cancer; DNA repair.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Ataxia Telangiectasia Mutated Proteins / antagonists & inhibitors
  • Autophagy
  • BRCA1 Protein / antagonists & inhibitors
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / physiopathology
  • DNA / metabolism
  • DNA Damage*
  • DNA Repair*
  • Female
  • Humans
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Poly(ADP-ribose) Polymerases / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction*

Substances

  • Antineoplastic Agents
  • BRCA1 Protein
  • BRCA1 protein, human
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Protein Kinase Inhibitors
  • DNA
  • Poly(ADP-ribose) Polymerases
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins