This week's headlines said we could have a 'revolutionary' drug for prostate cancer. What is this drug, and are PCR working on it?
First published 04/10/2019. UPDATED 24/4/2020 with new clinical trial results.
On Monday evening, the BBC reported on a “Revolutionary drug for prostate cancer,” The Times told us that “Precision pill olaparib could help thousands of men with prostate cancer,” and the Mail announced “Hope for thousands of prostate cancer sufferers as trial finds a ‘precision’ drug can help incurable patients live almost four months longer.”
These headlines were based on some encouraging news about a drug called olaparib, which emerged from the European Society for Medical Oncology conference (ESMO).
Some cancer cells have faulty DNA, and rely on a protein called PARP to help fix themselves. Olaparib is a drug which stops PARP from working. The cancer cells then can’t repair their faulty DNA and die. Normal, healthy cells don’t have the same defect that cancer cells do and so olaparib can target cancer cells more selectively than other cancer treatments can.
However, not every cancer has the kind of faulty DNA which makes it susceptible to being killed by olaparib.
Olaparib was originally discovered in the 1990s, in work supported by Worldwide Cancer Research, and is used by the NHS to treat ovarian cancer. It is sold under the name Lynparza.
Many researchers are investigating whether olaparib’s success so far can be replicated in other cancers.
The PROfound trial is looking at whether men with advanced prostate cancer, whose cancer cells can’t repair genetic mistakes very well, respond better to olaparib than they do to the latest forms of hormonal treatment (the drugs abiraterone and enzalutamide).
At ESMO, the scientists reported that using olaparib stopped cancer getting worse for about four months, men taking it spent less time in pain, and may have lived longer.
An expert called PROfound ‘a landmark trial,’ pointing out that the delay in cancer getting worse was considerably higher than in other trials – but she also cautioned that the final analysis was not yet ready, and that not all patients will be able to take olaparib.
These results are exciting because they show that olaparib might help men with advanced disease, and because it could be the first genetically targeted drug for prostate cancer.
On the 24th of April, 2020, the latest set of results from PROfound were announced. Olaparib improves overall survival compared to the hormone therapies abiraterone and enzalutamide in men with advanced prostate cancer which has already spread throughout the body, who have stopped responding to hormone therapy, and who have changes in their DNA known as BRCA1/2 or ATM mutations. Mutations like these, which mean cancer cells struggle to fix faulty DNA, are thought to occur in approximately 20-30% of advanced, hormone therapy resistant prostate cancers. The companies who produce this drug are working with regulators to get it to patients as quickly as possible.
We at PCR welcome this news, which is a fresh source of hope, and further proof that science is constantly moving forwards, towards a better future for anyone affected by prostate cancer.
One of our key goals is to support research which will help prostate cancer catch up with other cancers, which are recognised as being not one disease but a collection of diseases, and are treated in a much more targeted, effective way as a result.
Although we had no involvement with PROfound, its results directly relate to a separate study we are enabling as a result of our recent grant call.
Olaparib has potential to be a pathway to more personalised, effective treatment for prostate cancer patients. However, we could use olaparib and other drugs which work in the same way much better if we knew more about why they work in some men with prostate cancer but not in others.
Dr Harveer Dev is developing a radical new tool to address why some men with prostate cancer respond to DNA damaging drugs like olaparib and some don’t. Using prostate cancer cells donated by patients, Harveer will create ProCASP, which will be used in the lab to sharpen our understanding of a whole set of drugs which target DNA repair pathways inside a cancer cell, and help doctors identify which therapy will work best for which patient in the clinic.
ProCASP will be used to change DNA in prostate cancer cells. Then, the researchers can see which genetic changes help these drugs kill cancer, and which changes stop them from working. This research will help us find patterns in DNA that can be used to identify patients who will benefit from treatments like olaparib, and even radiation, which works by attacking cancer DNA.
Harveer is an academic urologist who cares for prostate cancer patients in the clinic and also conducts cutting-edge scientific research in the lab to understand why individual patients are resistant to treatment and how to overcome this.
“We are tremendously excited to work with PCR to deliver ProCASP. We will be establishing this first-in-kind system in order to explore how patient-derived cancers respond to existing and emerging therapies. This will allow us to identify individual patients who may benefit from specific early interventions. Our project represents an important step towards delivering personalised care and improving outcomes for patients with lethal disease.
Dr Harveer Dev
PCR Scientist