Synthetic Lethality

Inhibiting pathways that contribute to aberrant DNA repair and cellular metabolism

Accumulation of DNA damage, genomic instability, and altered cellular metabolism are pervasive characteristics of human tumors.1-3 Disruption of essential DNA damage repair or cellular metabolism in cancer cells may increase dependency on alternate repair pathways for cell survival or make tumors more susceptible to modulation of metabolic enzymes.2,4 Synthetically lethal therapies aim to combine pharmacologic inhibition of targeted pathways with tumor-inherent defects in key cellular processes that promote aberrant proliferation to selectively kill tumor cells while sparing healthy tissue.2,4-6 GSK is investigating a clinical asset that utilizes the power of synthetically lethal interactions to fight malignant cells in a variety of cancers.7

Niraparib
PARP inhibitor

MOA, mechanism of action; MOD, mechanism of disease; PARP, poly ADP ribose polymerase.

This document contains information for healthcare providers and is intended solely for educational purposes. This display includes ongoing clinical trials for both approved and investigational compounds. Some agents are approved in select indications. Inclusion in this display does not imply regulatory approval for these compounds or all indications. Information about all trials can be found at www.clinicaltrials.gov. All clinical study information updated as of April 10, 2023.

References: 1. Lord CJ, Ashworth A. Nature. 2012;481(7381):287-294. 2. O’Connor MJ. Mol Cell. 2015;60(4):547-560. 3. Coller HA. Am J Pathol. 2014;184(1):4-17. 4. Marjon K et al. Cell Rep. 2016;15(3):574-587. 5. Kelley MR et al. Future Oncol. 2014;10(7):1215-1237. 6. O’Neil NJ et al. Nat Rev Genet. 2017;18(10):613-623. 7. ClinicalTrials.gov. https://clinicaltrials.gov/. Accessed April 10, 2023.