Research at the University of Cambridge into DNA repair inhibitors led to a novel cancer therapy, Olaparib, which has been approved for ovarian, breast, pancreatic and prostate cancer treatment.
Stephen Jackson is a world-class pioneer in DNA damage repair mechanisms and was one of the first to attempt to translate his basic research in this area to drug discovery, recognising that faulty DNA damage repair pathways in cancers could be exploited therapeutically.
Alongside scientists at his spin-out company, KuDOS Pharmaceuticals, and collaborators at Cancer Research UK, Jackson showed that dysfunction of two genes known to increase cancer risk (BRCA1 and BRCA2) unexpectedly sensitises cells to the inhibition of PARP, a critical enzyme involved in DNA repair. This leads to chromosomal instability, cell cycle arrest and cell death. These findings led them to suggest a new approach for the treatment of patients with BRCA1- and BRCA2-associated cancers.
His discovery that DNA repair pathways could be targeted in cancer therapy led to the production of Olaparib, the world’s first marketed DNA-repair enzyme inhibitor. Olaparib is the first drug to exploit the principle of ‘synthetic lethality’, and the first cancer drug to target an inherited predisposition.
Olaparib has been used to treat over 30,000 patients in 73 countries, reducing disease progression and death by up to 66%.
Olaparib was valued at $17 billion in 2018 and in 2020 achieved an annual revenue of $1,776 million. So far, four companies, attracting significant investment, have been created to develop new drugs using this novel approach of DNA repair inhibitors to treat cancer, which has generated and supported over 70 jobs.
“Olaparib is a gamechanger in terms of treatment because it’s an easy drug to take in comparison with chemo. Without Olaparib, I basically wouldn’t be here. When I look back to that fourth lot of chemo when I said, “That’s it, I’m not doing it anymore – I can’t do it anymore”, and now, more than two years in, I live a pretty normal life. It’s hard to describe how wonderful that is.”
– Florence Wilks
