Synthetic lethality

With a clear vision and focus, we are leveraging synthetic lethality vulnerabilities to develop breakthrough solutions for cancers with high unmet medical needs.

What is synthetic lethality?

Synthetic lethality is a genetic concept that refers to a critical interaction between two genes. It occurs when the simultaneous loss of the function of both genes results in cell death, whilst the loss of only one of the two genes leaves the cells fully viable.

The recent development of gene-editing CRISPR technology have made it possible to carry out large-scale unbiased screens for such gene pairs directly in human cell cultures. When combined with data from next-generation sequencing of tumour tissues, it provides robust identification of synthetic lethality vulnerabilities for specific cancers.

Advantages of targeting synthetic lethality vulnerabilities

The principle of synthetic lethality provides a path to kill cancer cells while sparing healthy cells, thereby an opportunity for maximising therapeutic benefit while minimising undesirable side effects. It also has the advantage of being genetically defined, which means that genetic biomarkers can be used to select patients who are most likely to respond to the treatment.

Translation of synthetic lethality to therapy

Therapeutic blocking of a functional protein within a synthetic lethality pair can efficiently be achieved with a small molecule inhibitor. By applying our validated technology platform, we discover and develop novel small molecule therapeutics across multiple modalities, including allosteric inhibitors and targeted degraders.

Combining a validated approach with fundamental expertise 

Our drug development strategy focusses on targeting genetically defined cancers with synthetic lethality vulnerabilities. We utilise our established drug discovery and development platform, enhanced by the passionate and dedicated team of scientists and development professionals, to methodically identify targets and advance our pipeline of promising and proprietary small molecule therapeutics.

Further reading

  • Huang A et al. (2020) Synthetic lethality as an engine for cancer drug target discovery. Nat Rev Drug Discov, 19(1):23–38.
  • O'Neil NJ et al. (2017) Synthetic lethality and cancer. Nat Rev Genet, 18(10):613–623


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