Cambridge BRC scientists report promising new findings on early use of targeted therapy in prostate cancer
Dr Simon Pacey (left) Academic Medical Oncologist. Dr Harveer Dev (right) Academic Urologist. Credit: CRUK Cambridge Centre
17 June 2025
A Cambridge-led clinical trial, supported by the Cambridge BRC, has revealed how a short course of targeted therapy prior to surgery can influence the biology of prostate cancer – even in men who do not carry known DNA repair gene mutations.
The findings, published in the scientific journal Clinical Cancer Research, represent a key milestone for a team of translational scientists and clinicians in our Urological Malignancies Virtual Institute. They are aiming to introduce targeted therapies earlier in the prostate cancer treatment pathway to improve patient outcomes.
The trial, known as CANCAP03, studied the effects of two drugs – the PARP inhibitor olaparib and a testosterone-blocking agent degarelix – administered before planned prostate surgery.
Medications olaparib and degarelix used in the CANCAP03 trial. Credit: CRUK Cambridge Centre.
CANCAP03 was led by Dr Simon Pacey, Academic Medical Oncologist and expert in early drug development with Dr Harveer Dev, Academic Urologist and Group Leader at the Early Cancer Institute. They worked in partnership with AstraZeneca (Partner of Choice), supported by Prostate Cancer Foundation and John Black Charitable Trust, to design the ‘window-of-opportunity’ clinical trial, where patients are given treatment in the time period between their diagnosis and surgery.
For the CANCAP03 trial, men with higher-risk, localised prostate cancer were recruited from three UK centres – in Cambridge, London and Cardiff. Tumour samples taken before and after the targeted therapy treatment. This provided an unprecedented analysis of how the drugs worked on the cancer cells. The results showed that the combination of the two drugs altered cancer cell behaviour in ways not previously observed in preclinical studies or monotherapy settings – notably affecting cancer cell growth, inflammation, and DNA damage response signalling.
Dr Dev said:
“These are the first human data showing how this combination works directly within prostate tissue. Remarkably, we saw effects in men without BRCA or other homologous recombination mutations,”
“This opens up the possibility of using PARP inhibitors in a broader group of patients – not just those with known DNA repair defects, through our better understanding of the mechanism of action.”
Importantly, the treatment was well tolerated, did not delay surgery, and yielded high-quality samples for downstream molecular analysis.
Dr Pacey said:
“This study is a powerful example of how early-stage translational trials can both inform science and benefit patients,”
“Our ability to recruit and complete this work reflects the strength of our clinical trials ecosystem in Cambridge and the generosity of our patients.”
This study was supported by the Cancer Molecular Diagnostics Lab (CMDL) which is funded by the Cancer Research UK Cambridge Centre and NIHR Cambridge Biomedical Research Centre. The lab carried out the genetic analysis on the tumour samples to identify the mutations in tumours from these patients. All of the DNA and RNA extractions, followed by genetic analysis using next generation sequencing (NGS), were performed with CMDL’s 350 gene pan-cancer panel.
The findings laid the groundwork for a larger, multi-site international study, called ASCERTAIN, which is now underway, co-led by Dr Pacey and Dr Mateo, from the Vall d’Hebron Institute of Oncology in Spain.
Meanwhile, the Dev lab continues to explore mechanistic insights into the interaction between androgen signalling and DNA repair, backed by competitive funding awards from the Prostate Cancer Foundation, Prostate Cancer Research, Prostate Cancer UK, and in partnership with AstraZeneca.
Dr Pacey said
“Ultimately, this is about delivering precision medicine at the earliest stages of disease,”
“Through strategic partnerships with industry and the Urological Malignances Virtual Institute, we’re building the next generation of clinical trials to better define who benefits from which therapies – and when.”
The team envisions this work contributing directly to Cambridge Cancer Research Hospital, aiming to offer genetic testing and make clinical trials available to all men diagnosed with prostate cancer in the East of England.
Read more about prostate cancer research in Cambridge and the ASCERTAIN trial
