For Damaged DNA In Cancer Cells, Scientists Now Have Solution

73

Impressive developments are happening fast in the world of science these days. Amazingly, scientists have developed a new “precision medicine” approach to treating the damaged DNA in the cancer cells of Pancreatic Cancer patients.

The findings mark an important step forward for potential treatment options for pancreatic cancer, improving the options and outcomes for a disease where survival rates have remained stubbornly low.

The study detailing the approach—led by the University of Glasgow and published in Gastroenterology—used cell lines and organoids that were generated from patients with pancreatic cancer to develop new molecular markers that can predict who will respond to drugs targeting DNA damage.

The researchers tested these markers using multiple drugs, and have developed a strategy that are now being taken forward into a clinical trial. The trial will help doctors and researchers predict which patient will respond to which one of these drugs, either alone or in combination.

Funding for the trail has come from AstraZeneca and will now be included in the PRIMUS-004 clinical trial as part of the Precision-Panc therapeutic development platform for pancreatic cancer.

PRIMUS-004 is a ground-breaking pancreatic cancer trial, which aims to match patients with more targeted and effective treatment for their tumours. Run by Precision-Panc, a flagship therapeutic development program dedicated to pancreatic cancer—led by the University of Glasgow with major funding from Cancer Research UK—the trial brings a precision medicine approach to pancreatic cancer treatment for the first time in the UK.

The trial will open for recruitment in Glasgow shortly, with 20 other centres throughout the UK to follow.

Although survival for many types of cancer has improved, pancreatic cancer survival has lagged significantly behind in the last 40 years. The disease is particularly hard to treat, partly because it’s often diagnosed at a late stage.

A major limitation to treating pancreatic cancer effectively is that there are very few treatment options for patients with the disease.

Currently, some patients with pancreatic cancer cannot repair damaged DNA in the cancer cells, which makes the cancer vulnerable to some new and established drug treatments.

Dr. David Chang, from the University of Glasgow’s Institute of Cancer Sciences, says “our study is a huge breakthrough in terms of what might be possible with future treatments. As part of our research, the strategy we’ve developed is extremely promising, and we’re very pleased and proud to see it now be taken into clinical trial. For us, this is a demonstration of a bench-to-bedside precision oncology approach to tackle this terrible disease.”

Michelle Mitchell, Cancer Research UK’s chief executive, said “we urgently need new ways to treat pancreatic cancer. The disease only has a few treatment options and is generally diagnosed at a late stage, so survival has remained stubbornly low.

‘’The Precision Panc study offers a dynamic way to explore new tailored treatments, and it’s fantastic that we now have new drug candidates to add to the PRIMUS-004 trial. We look forward to seeing if these drugs, which have shown promise in the lab, have the same impact for people with pancreatic cancer.”

Funding for PRIMUS 004 has been obtained from AstraZeneca and the study has been endorsed by Cancer Research UK. The trial is being coordinated by the Cancer Research UK Glasgow Clinical Trials Unit.

The paper, Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer, is published in Gastroenterology.

Before this development, there was a groundbreaking pancreatic cancer trial, which aims to match patients with more targeted and effective treatment for their tumours, successfully recruited its 100th patient.

Run by Precision-Panc, a research programme and clinical trials project led by the University of Glasgow with major funding from Cancer Research UK, the trial brings a precision medicine approach to pancreatic cancer treatment for the first time in the UK.

Pancreatic cancer is the fifth most common cause of cancer death in the UK with a 5-year survival rate of less than 3%. Around 9,800 people are diagnosed with pancreatic cancer per year in the UK and around 9,000 people die.

In December 2017 Precision-Panc began working alongside colleagues in NHS Greater Glasgow and Clyde Health Board to recruit suitable pancreatic cancer patients to the Precision-Panc Master Protocol at Glasgow Royal Infirmary.

The Glasgow-born project has been so successful in the last year, it has now been rolled out to 16 sites across the UK, offering potential treatment hope for pancreatic cancer patients nationwide.

As part of the protocol, each patient undergoes tumour biopsy to obtain material that is then used for molecular profiling at the Glasgow Precision Oncology Laboratory (GPOL) within the University of Glasgow. The results may then be used to help match patients to the most appropriate, currently available clinical trial.

This ability to link clinical data with the patient’s unique molecular profiling data enables rapid new discoveries, and enhances the delivery of precision medicine to current and future patients.

Professor Andrew Biankin, Chief Investigator of Precision Panc and Regius Chair of Surgery and Director of the University of Glasgow Wolfson Wohl Cancer Research Centre, said: “I am extremely proud of what we have been able to achieve so far with Precision Panc. Recruiting the 100th patient is a milestone for us and signals our ability to make real changes to the lives and survival rates of patients with pancreatic cancer.

“The success we have achieved so far – including opening 17 sites across the country – is testament to what we are able to achieve and deliver for patients as a team.”

The overall aim of PRECISION Panc is to make precision medicine a reality for more people with pancreatic cancer through building up knowledge that will ultimately allow clinicians to match patients with the most suitable treatment or clinical trial for them. The project aims to facilitate drug development, and ultimately new drug approval, allowing access and improving survival in patients with pancreatic cancer.

Dr. Ian Walker, Director of Clinical Research at Cancer Research UK, said: “To make real progress in improving survival for people with pancreatic cancer, we need to understand which drugs will be most likely to provide benefit for individual patients. Through Precision-Panc, we are looking to do just that, and recruiting 100 patients is a huge landmark for this ambitious study.

“While overall survival from cancer has doubled over the last 40 years, pancreatic cancer has only seen little improvement, and too many people die from the disease each year. Innovative studies like Precision-Panc are vital to changing the outlook for these patients and we look forward to seeing how it continues to progress.”

About Precision-Panc and the PRIMUS Trials

The Master Protocol serves as the entry point to Precision-Panc and is the first step for patients to be recruited before enrolling onto a suitable clinical trial.

Three clinical trials, funded in part by Cancer Research UK, will recruit a total of 658 pancreatic cancer patients under the Precision-Panc umbrella, with scope to add more trials in the future. Each clinical trial will test new drugs and combinations of drugs tailored to match specific patients.

Precision-Panc is an ambitious programme of research that seeks to uncover the molecular profile of individual patients with pancreatic cancer, to learn more about the disease and to pave the way for patients entering clinical trials in a way that matches their tumour biology to the type of treatment.

It is composed of a network of clinical trials aimed to find the right trial for the right patient matching patients to treatments most likely to work for their type of pancreatic cancer. It is designed to be comprehensive with a faster turnaround time than traditional clinical trials while advancing discovery through science and ultimately changing patient outcomes in this disease.

Precision-Panc is a collaborative effort between clinicians, scientists and various other experts with key partnerships between the NHS GGC Biorepository, Molecular Genetics West of Scotland Genetic Services based at the Queen Elizabeth University Hospital, the Glasgow Precision Oncology Laboratory at the Wolfson Wohl Cancer Research Center, University of Glasgow, Beatson Institute for Cancer Research, and the CRUK Clinical Trials Unit formed to carry out tissue acquisition, storage, processing, testing and analysis.

PRIMUS-001 (Pancreatic Cancer Individualized Multi-arm Umbrella Study) is an adaptive Phase II/III study with an integrated biomarker evaluation in patients with metastatic disease and is currently open at 11 sites around the UK.

PRIMUS-002 will aim to define biomarkers of therapeutic responsiveness in the neoadjuvant setting and opened in Glasgow in March 2019. Celgene International supports both of these studies.

Additionally, PRIMUS-003, supported by AstraZeneca, is using an immunotherapy approach and is also currently recruiting patients in the metastatic setting. If appropriate, as part of the Precision-Panc Master Protocol, patients may also be helped onto other suitable clinical trials that are already up and running across the UK.

 

LEAVE A REPLY

Please enter your comment!
Please enter your name here