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Synthetic lethality on drug discovery: an update on cancer therapy

M Shahar Yar1, Kashif Haider1, Vivek Gohel2

  • 1Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard , New Delhi, India.

Expert Opinion on Drug Discovery
|April 2, 2020
PubMed
Abstract

Insights

Synthetic lethality (SL) offers a novel approach to overcome cancer chemotherapy resistance by exploiting specific gene mutations. This strategy targets vulnerabilities in cancer cells, leading to cell death when two DNA repair genes are simultaneously impaired.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Growing resistance to conventional chemotherapy necessitates novel anticancer therapies.
  • Synthetic lethality (SL) is an emerging strategy that exploits cancer cell-specific genetic vulnerabilities.
  • SL involves targeting two genes where the loss of function in either gene is tolerated, but the loss of function in both leads to cell death.

Purpose of the Study:

  • To review and condense findings on synthetic lethality-based novel anticancer regimens.
  • To highlight preclinical and clinical studies of novel targets and therapies utilizing the SL approach.
  • To discuss the potential of SL in combating resistance to existing anticancer agents.

Main Methods:

  • Review of existing literature on synthetic lethality in cancer therapy.
  • Analysis of clinical and preclinical studies focusing on SL-based novel targets and treatments.
  • Examination of the role of DNA repair pathways in synthetic lethality.

Main Results:

  • Synthetic lethality offers a promising strategy to address treatment resistance in cancer.
  • Numerous clinical trials are investigating SL-based therapies and their associated biomarkers.
  • SL-based approaches are paving the way for personalized medicine in oncology.

Conclusions:

  • Synthetic lethality represents a significant advancement in developing new anticancer regimens.
  • The continued exploration of SL will enhance our understanding of cancer vulnerabilities and drug effectiveness.
  • SL-based strategies are expected to drive the development of personalized cancer medicines.
Keywords:
BRCAPARPSynthetic lethalitycancer

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