Scientists from the University of Glasgow are developing new ways to predict who will respond to drugs targeting damaged DNA in pancreatic cancer.
Publishing their findings in Gastroenterology, the team used cells grown in the lab (cell lines) and mini replicas of patients’ tumours (organoids) to identify molecular markers that can predict which tumours will respond to a number of drugs that target damaged DNA.
Dr David Chang, from the University of Glasgow’s Institute of Cancer Sciences, called the results “a huge breakthrough in terms of what might be possible for future treatments.”
The team are now taking their strategy forward into a clinical trial to help doctors work out who might respond to the drugs, either alone or in combination. The trial – PRIMUS-004 – is part of our Precision Panc platform for pancreatic cancer, which aims to increase opportunities for people with pancreatic cancer to join clinical trials and to develop new treatment strategies.
In 2017, Cancer Research UK invested £10 million in Precision Panc to speed up understanding of pancreatic and work towards more tailored treatment for the disease. It’s the charity’s biggest standalone in pancreatic cancer research to date, with the aim of driving progress for pancreatic cancer, where survival has remained stubbornly low.
A major barrier to treating pancreatic effectively is that there are very few treatment options. But there are some pancreatic cancers that cannot repair damaged DNA, which make them vulnerable to some new treatments. This is what researchers are aiming to target.
“We urgently need new ways to treatment pancreatic cancer,” says Michelle Mitchell, Cancer Research UK’s chief executive. “The Precision Panc study offers a dynamic way to explore new tailored treatments, and it’s fantastic that we know have new drug candidates to add to the PRIMUS-004 trials.”
A menu of trials
PRIMUS-004 is a mid-stage (phase 2) clinical trial testing the new approach to help match people with pancreatic that’s spread to new targeted treatments.
The trial is due to open this month and will be an option for people who’ve already had platinum chemotherapy and whose cancer has a fault that means it cannot repair damaged DNA. Funded by AstraZeneca and endorsed by Cancer Research UK, it’s the first trial in the UK that will test this precision medicine approach in pancreatic cancer.
PRIMUS-004 is the fourth trial that Precision Panc will feed into, with 3 studies already linked to the platform – PRIMUS-001 for people with pancreatic cancer that’s spread and PRIMUS-002, which is testing the benefits of 2 different chemotherapy combos before surgery.
Another trial – PRIMUS-005, involving patients with locally advanced cancer – is also due to open this month.
As well as helping to give people with pancreatic cancer better trial options, the Precision Panc study is also collecting and analysing tumour samples and looking for new biomarkers to help researchers predict which treatment might work best.
So far 331 people have entered the Precision Panc platform from 27 sites around the UK. And while COVID-19 paused recruitment earlier this year, most centres have managed to reopen and 14 people joined the study in September 2020, only slightly below pre-COVID levels.
Dreyer, S et al. (2020) Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer. Gastroenterology. DOI: https://doi.org/10.1053/j.gastro.2020.09.043