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Predicting which men will benefit from olaparib

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Grant information

Researcher – Prof Johann de Bono
Institution – Institute of Cancer Research
Grant award - £315,895
Duration - 2015-2018
Status - Complete
Reference – PG14-010-TR2

We have shown that there are many different types of prostate cancers, increasing complexity for doctors, with very different hijacked genomic switches; some of these impact DNA repair and are tumour cell vulnerabilities, allowing us to deliver personalised precision medicines that have improved care.
Professor Johann de Bono

Why did we fund this project?

  • Professor Johann de Bono and team have carried out a clinical trial called 'TOPARP', to show that a drug called olaparib is effective at slowing the growth of prostate cancer in about 30% of men.
  • In this project, the team wanted to work out why this subset of men responded to olaparib, and others didn't.
  • The team thought that certain changes in the genes of cancer cells, known as mutations, might give some men's cancer an 'Achilles' heel' that could be exploited by olaparib.
  • In this project, the team aimed to identify exactly which mutations constituted this Achilles' heel .
  • They aimed to develop a simple test that could identify men who would benefit from olaparib, enabling treatment to be effectively targeted.

What did the team do?

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  • The team studied the genes in prostate cancer samples from men who took part in the TOPARP trial, to determine which mutations were most closely linked to the effectiveness of olaparib.
  • The team also studied blood samples, to test whether the mutations could be detected by a simple blood test.

What did the team achieve?

  • The team found that mutations that predicted whether men would respond to olaparib could be detected in the blood.
  • This meant the team could identify men who are most likely to benefit from olaparib to recruit for a larger trial called 'PROFOUND', to test the drug in advanced prostate cancer.
  • This trial has now been completed, and it's success means olaparib is now a targeted treatment option for some men with advanced prostate cancer, who also have mutations in certain genes.
  • Read our impact case study on how our researchers contributed to olaparib becoming the world's first precision medicine for prostate cancer.

How does this benefit men?

  • The team's work gave insight that led a new treatment option becoming available that can help some men with advanced prostate cancer live longer.
  • Identifying mutations linked to response to olaparib has allowed the treatment to be targeted, so that only those who are likely to benefit are prescribed olaparib.
  • The team are now studying ways to predict how men's cancer will respond to other prostate cancer treatments, so all men can get the most effective therapy tailored to them.
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