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PRIME time: how team science is bringing liquid biopsies into the clinic for prostate cancer

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by Cancer Research UK | Research Feature

20 September 2018

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An international team of oncologists, computational and translational researchers, funded through the Accelerator Award, is developing novel tools to analyse liquid biopsies for prostate cancer. We talked to its lead investigator, Professor Francesca Demichelis, and learnt about how this multidisciplinary team is changing the treatment landscape for the most common type of cancer in men.

Reaching patients through a wide clinical network

Led by Professor Francesca Demichelis at the University of Trento in Italy, research and clinical groups across Italy and the UK are coming together to bring precision medicine to prostate cancer. PRIME (Prostate cancer plasma Integrative multimodal evaluation) aims to maximise the amount of information that can be generated from liquid biopsies, expanding their clinical uses in molecular stratification, treatment selection, and monitoring resistance.

Heading-up the project in the UK is Professor Gerhardt Attard – a Cancer Research UK Advanced Clinician Scientist Fellow based at the University College London Cancer Institute, whose group has been collecting high quality liquid biopsies from clinical trials of advanced prostate cancer, including the UK-wide, practice-changing STAMPEDE clinical trial for men starting long-term life-prolonging hormone therapies. Gerhardt and Francesca started collaborating more than five years ago, after meeting at the American Association for Cancer Research annual meeting in 2011.

Together they started working on the project and building an extensive network of collaborators at multiple clinical centres running prostate cancer trials in both the UK and Italy. This gives the team access to cases representative of the whole spectrum of advanced prostate cancer, including hormone-sensitive disease and through to men who have developed treatment resistance. Francesca plans to tap into the expertise these trials have accumulated over the years to develop and test PRIME.

Increasing the sensitivity of liquid biopsies

Liquid biopsies have been gaining ground in recent years because they are non-invasive and can be obtained repeatedly, but their molecular outputs are not yet as extensive as those from tissue biopsies.

That’s where PRIME comes in. By increasing the analytical powers of liquid biopsies for prostate cancer, Francesca hopes to be able to develop a tool with the potential to monitor tumour response to treatment in real-time.

What I’m most excited about is that we will be exploiting every level of molecular information from patients’ tumour-derived material that is in the blood. That’s something that isn’t currently done. We’re pushing the sensitivities of the assays in genomics, transcriptomics and methylation.

Francesca reckons, the main challenges will be figuring out how to generate the data from the test, and then how to analyse it computationally.

“The moment we have something that’s analytically robust, it can be used by clinics and by our clinical collaborators for their own research. Anyone who wants to use it when it’s ready can run their own translational research study using PRIME. It’s accelerating clinical cancer research and gives independence to the clinical sides to do what they feel is important in research based on their trials, their collaborators and their work.”

Advice to future applicants: Get together to talk about your application

Francesca believes that there were two reasons why her application was successful.

“We had strong preliminary data that showed the feasibility of what we wanted to do. It showed that we had really thought through our application. We also got together in the same room with all collaborators and I think that was key. This came across during our interview for the Accelerator Award as we demonstrated that we had discussed the project in detail and thought about what we wanted to achieve.”

She recommends that anyone thinking of applying for the Accelerator Awards should get together with their collaborators to discuss the ins and outs of their proposal. Francesca and Gerhardt’s history of fruitful collaborations certainly helped when it came to designing a competitive and fundable project:

“Having worked together before gave us the confidence that we could do so now – whilst also knowing for sure that what we were proposing would work. It allowed us to be extra novel in our proposal.”

Her advice to applicants is:

“Think broadly, but make sure you keep your feet on the ground. You need to know what you can deliver in five years. During the interview, they really wanted us to explain how we would be able to deliver, so make sure that you’re practical about it.”