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YCR funded drug, olaparib, shows great promise.

ycr-scienceA drug called olaparib – where YCR funded the initial development – has shown great promise when given together with another chemotherapy drug, potentially doubling the amount of time people can survive, whilst also improving medication related side effect issues.


Following on from a previous blog about the developments in anti-PD1 drugs announced at ASCO 2014 comes news of another promising development. At the same meeting AstraZeneca announced promising results from a trial of a drug called olaparib.


This is of special importance because YCR funded early work on olaparib at the University of Sheffield, and the work has progressed to clinical trials with AstraZeneca (who were in the news recently due to a recent takeover bid from Pfizer). It is good to see work that YCR started being taken on and developed further through the process of drug development.


Olaparib has already shown great promise as a treatment against cancers, but recently a Phase II study in the USA  showed that using olaparib in combination with a drug called cediranib could almost double the amount of time that cancer could be stopped from getting worse to almost 18 months, compared to 9 months in patients using just olaparib.


How olaparib works



Before discussing olaparib itself we need to know about two genes called BCRA1 and BRCA2; these are DNA-repair proteins which protect cells from mutations. Some people are born with mutations in these genes and these people are more susceptible to getting cancer. However, this also gives the cancer cells a unique vulnerability which olaparib exploits to kill the cancer cells.


Cells have backup systems which repair our DNA; PARP1 is another enzyme that  repairs DNA, similar to BRCA1 and 2. Olaparib works by stopping PARP1 from working and so is known as a “PARP inhibitor”. In healthy cells, other proteins like BRCA1, 2, and PARP work together to keep cells alive. However, when a cancer cell with broken BRCA1 and 2 is given olaparib, the cell loses the ability to repair its DNA, which rapidly leads to cell death. This is because small breaks called “nicks” accumulate in the the DNA before the cell divides. This is important because if the cell divides while it has a nick in its DNA, the new cells will die. Cancer cells are fast-dividing and so die rapidly.


How close are we to hospital treatment?



Olaparib has moved into Phase III trials as an individual treatment to assess how much better than existing treatments it is. In addition, it is currently going through regulatory approval and has been granted priority review by the Food and Drug Administration in the US, which will accelerate the process for approval.  We expect to hear the results of this by October 2014. Something that falls in favour of olaparib is that it is proving to have fewer side-effects when used alongside chemotherapy drugs, which is an additional benefit alongside its effectiveness.

It is good to see a drug where YCR funded the initial development, with the view of providing benefits to cancer patients.


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