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Reverse the Resistance to PARP Inhibitors

Yevgeniy Kim1, Aleksei Kim1, Ainur Sharip1

  • 1Department of Biology, Nazarbayev University, School of Science and Technology, Astana, 010000, Republic of Kazakhstan.

International Journal of Biological Sciences
|March 4, 2017
PubMed

Insights

Poly (ADP-ribose) Polymerase (PARP) inhibitors are vital cancer treatments. This review details recent molecular mechanisms of PARP inhibitor resistance and strategies to overcome it.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Poly (ADP-ribose) Polymerase (PARP) enzymes are crucial for DNA repair, particularly single-strand breaks.
  • PARP inhibitors (PARPi) are established as a valuable addition to conventional chemotherapy for cancer treatment.
  • Acquired resistance to PARPi poses a significant challenge in clinical oncology.

Purpose of the Study:

  • To elucidate the latest molecular mechanisms underlying resistance to PARP inhibitors.
  • To summarize emerging strategies for reversing PARP inhibitor resistance in cancer therapy.

Main Methods:

  • Literature review of recent studies on PARPi resistance.
  • Analysis of molecular alterations and genetic events conferring resistance.
  • Synthesis of data on therapeutic approaches to overcome resistance.

Main Results:

  • Identified several novel molecular mechanisms driving PARPi resistance, including specific gene mutations and pathway alterations.
  • Documented various strategies, such as combination therapies and targeting resistance pathways, to restore PARPi efficacy.
  • Highlighted the dynamic and complex nature of resistance development.

Conclusions:

  • Understanding the molecular basis of PARPi resistance is critical for developing effective treatment strategies.
  • Targeting resistance mechanisms offers promising avenues to improve patient outcomes in PARPi-treated cancers.
  • Further research is needed to translate these findings into clinical practice.
Keywords:
DNA repairPARPPARP inhibitordrug resistance

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