Olaparib – a research success story
Worldwide Cancer Research funds pioneering ideas at the very beginning of the cancer research journey as we know that is where the next big breakthroughs will happen - by delving into the unknown. We understand that the path of research is often unclear and the eventual outcomes can never be predicted. For example, when we awarded a series of grants to Professor Steve Jackson back in the last 1990's to study DNA damage and repair we could never have predicted that many years later we would have helped in the early development of a brand new cancer drug, olaparib.
What is olaparib?
Olaparib is the first in a brand new class of cancer drug called PARP inhibitors. PARP inhibitors work by exploiting a defect some cancers have in a particular type of DNA repair. Because healthy cells don’t have this defect, olaparib is able to target and kill cancer cells more specifically than normal chemotherapy drugs can.
Olaparib, developed by AstraZeneca, was first licensed in late 2014 by the FDA in the USA, and by the EMA in Europe, for the treatment of advanced ovarian cancer. It has since been approved for use in the UK by the National Institute of Health and Care Excellence (NICE) and Scottish Medicine's Consortium.
Who can benefit from the drug?
Women with ovarian cancer who have had three rounds of conventional chemotherapy and who have a mutation in the BRCA1 or BRCA2 genes will be able to get olaparib. In clinical trials, olaparib extended the progression free survival of women with advanced ovarian cancer by an average of several months, and some women benefited much more than this. It will also be used to treat women with fallopian tube and peritoneal cancers.
How did Worldwide Cancer Research help?
In the mid-1990s we gave grants to Professor Steve Jackson in Cambridge for a series of projects studying DNA repair. He used findings from these projects, along with others, to set up a company called KuDOS Pharmaceuticals Ltd. Worldwide Cancer Research (or AICR as we were then) received shares in the company to recognise the contribution of our grants. KuDOS went on to develop olaparib, a drug targeting DNA repair – labelled ‘first in class’. KuDOS was taken over by AstraZeneca in 2005, at which point AstraZeneca took over testing of the drug.
Our story doesn’t stop there. Later, in the mid-2000s, we funded Professor Alan Clarke to test olaparib in a new mouse model of breast cancer. His work supported the case for using olaparib in cancers with BRCA mutations and helped olaparib on its way to clinical trials.
Dr Helen Rippon, Chief Executive, commented:
“Ovarian cancer lags behind other cancers when it comes to the availability of modern, targeted treatments and the prognosis for women diagnosed with ovarian cancer is often poor. That is why we are so pleased to have been involved in the development of this new treatment. Olaparib is a brilliant example of how laboratory research into basic cancer cell mechanisms – in this case DNA repair – can lead many years later to a new cancer drug. Worldwide Cancer Research is proud to have played a part in that early development."
What next for olaparib?
Olaparib is in clinical trials for a wide range of cancer types, including breast, pancreatic, oesophageal (foodpipe), head and neck, glioblastoma brain tumours, lung cancer, leukaemia and mantle cell lymphoma. Promising findings were also recently announced from a clinical trial in prostate cancer. Needless to say, we will be paying very close attention to the outcomes. And, as research progresses, we have every hope that in future, olaparib will prove to be useful in treating these other diseases as well.
Image source: AstraZeneca PLC
Written by Dr Gwen Wathne and Dr Helen Rippon