Research blog: The jigsaw is falling into place but one crucial piece is missing

The ASCO conference is always packed with exciting cancer research and this year we’ve seen a number of advances in prostate cancer, including work funded by us, that are at the cusp of transforming men’s lives.

First targeted treatment close to reaching clinics

For me, one of the conference highlights (and this is, of course, an unbiased opinion!) was a presentation of the results of TO-PARP B, a clinical trial part-funded by Prostate Cancer UK and The Movember Foundation.

This trial tested olaparib, a drug that was developed for ovarian and breast cancers, but researchers have since found that it can treat some men with prostate cancer that’s resistant to hormone therapy.

This type of drug, known as PARP inhibitors, work by exploiting cancer’s need to constantly repair damage to DNA. There are two main routes that they use to do this. PARP inhibitors block one route, but they can only work in men whose cancer has a genetic mutation that stops the other route too. The TO-PARP B trial delved into which men, with which DNA repair defects, respond best to olaparib.

This kind of trial is exciting because it represents the dawn of a precise approach to treating prostate cancer where men and their cancers will be treated as individuals rather than with a ‘one-size-fits-all’ approach.

This precision medicine tactic has been used in other cancers for many years, and now we’re working to bring this to men with prostate cancer too. That’s exactly why we chose to fund the TO-PARP trial in 2014, and why we’ll continue to champion precision medicine.

The results of the trial presented this week showed that 80 per cent of men with certain DNA repair defects in the BRCA1/2 genes responded to olaparib treatment, with a weaker effect for other DNA repair mutations.

Building on the momentum from the TOPARP trial, phase III clinical trials of PARP inhibitors are well underway and we expect to see results in the next 12 months. If those large trials confirm the results we’ve already seen, it’s likely that we’ll have the very first precision medicine for men with prostate cancer.

Enzalutamide joins the frontline

Another standout development for me was the trial that showed the drug enzalutamide could extend the lives of men newly diagnosed with advanced prostate cancer.

Enzalutamide is already available to men when their cancer becomes resistant to hormone therapy, but this week’s results show the drug could also be beneficial when taken alongside hormone therapy, when men are first diagnosed with the disease. You can read more about that here.

The announcement marks the third new treatment for this group of men in four years, alongside docetaxel and abiraterone. In fact, results demonstrating that a fourth drug, apalutamide, is likely to enter this space were also presented at ASCO.

Finding cancers to target with a nuclear payload

My final highlight was another treatment for advanced prostate cancer, ¹⁷⁷Lu-PSMA-617. It delivers a radioactive payload specifically to prostate cancer cells by targeting the PSMA protein, which is only found on prostate cancer cells. That means the treatment can circulate the body, picking off the cancer and leaving everything else unharmed.

This therapy is only just into Phase III clinical trials to test how well it works, but even before this research finishes, scientists are working to define who the treatment will work for.

At the moment, this involves a special type of imaging to identify tumours with high levels of PSMA. But results presented this week suggest we might need a better way. The researchers found that not every man, or even every cell within a single cancer site, has the same level of PSMA. On the other hand, another study showed some men with no visible PSMA still responded to the treatment.

Together these results build a case for just how important it is to understand the unique traits of each man and his cancer, and how these could interact with his treatment.

The researchers also found men whose cancers had high levels of PSMA tended to be the same men who had mutations in their DNA damage repair genes. It suggests ¹⁷⁷Lu-PSMA-617 might work well when combined with different treatments, like PARP inhibitors. In fact, we’ve already funded research looking at combining PSMA-targeted radiotherapy with other treatments that might help provide those answers over the next few years.

The missing piece of the jigsaw

It was clear from all the research presented at the conference that we’re seeing huge and rapid progress in options for treating advanced prostate cancer, with multiple new treatments on the verge of hitting the clinic.

This is great news for men but one crucial piece in this particular jigsaw is still missing. These new treatments may on the face of it seem completely different, but they all have one thing in common: we need a precision treatment approach.

We know not every man responds the same to each of these treatments, so now we’re leading the way to a precision medicine approach for treating men with advanced prostate cancer.

That’s why, in 2017, we launched our precision medicine programme, to give us a greater understanding of the genetics of each man and his cancer, and how this can be used to give him the best treatment possible.

With the help of supporters like you, we’ll continue to champion precision approaches to treatment and research that gets more out of trials, to give all men the best outcome from prostate cancer possible as soon as possible.