Cambridge researchers to receive nearly £4m to tackle cancer roadblocks

NIHR Cambridge BRC researchers are among the Cambridge scientists to receive £3,938,500 as part of Cancer Grand Challenges, a major initiative co-founded by Cancer Research UK and the National Cancer Institute in the US, which aims to encourage the world’s leading cancer researchers to take on some of the toughest challenges in cancer research.

The eDyNAmiC (extrachromosomal DNA in Cancer) team will investigate new ways to combat treatment resistant cancers, while the CANCAN (CANcer Cachexia Action Network) team hopes to prevent cachexia, where patients ‘waste away’ in the later stages of their disease.

Funding for the Cambridge-based projects is part of an overall £80 million awarded this week to four elite global teams who will deepen our understanding of cancer through international collaboration leading to new advances for people with cancer.

Extrachromosomal DNA – present in up to a third of all tumours, helps to evade treatment

The Stanford University-led eDyNAmiC team, which includes Professor Serena Nik Zainal at the University of Cambridge, hopes to tackle tumour evolution, which is driven by circular pieces of tumour DNA which exist outside the tumour and pose a major problem by enabling tumours to resist treatment.

Research is now revealing that a major driver of tumour evolution is extrachromosomal DNA (ecDNA). These small circular DNA particles enable cells to rapidly change their genomes and so evade the immune system.

EcDNA doesn’t follow the rules of normal chromosomes, providing tumours a way to evolve and change their genomes to evade treatment.  

Although first observed in cancer in 1965, researchers are only beginning to understand the extent to which it is prevalent in around a third of cancers and how it helps tumours to become more resistant, aggressive and affect patient survival.

The goal of eDyNAmiC is to understand how extrachromosomal DNA is created, to find vulnerabilities and then to develop new ways to target these in some of the hardest cancers to treat, including glioblastoma, lung and oesophageal cancer.

Co-investigator Professor Nik-Zainal (pictured, below), of the University of Cambridge Early Cancer Institute and Department of Medical Genetics, said: “My team and I are so excited to be part of this collaboration studying this phenomenon of extra pieces of DNA called ecDNA.

“What a privilege it is to be entrusted to explore how ecDNAs cause cancer and drive them to be aggressive. We hope that what we learn will bring real benefits to cancer patients in due course.”

Research aims to improve quality of life for patients with cancer cachexia

The CANCAN team is led by US researchers who will work with co-investigators Professor Sir Stephen O’Rahilly and Dr Tony Coll, of the Wellcome-MRC Institute of Metabolic Science, and Dr Giulia Biffi, of the CRUK Cambridge Institute, to explore the underpinning mechanisms behind cancer cachexia – a debilitating wasting condition many people experience in the later stages of the disease.

Cachexia syndrome is characterised by poor appetite and extensive weight loss from both skeletal muscle and fatty tissue and is still not fully understood.

It is hoped further research can help develop new treatments to improve quality of life for cancer patients and set the standard for cachexia management around the world.

Professor Sir Stephen O’Rahilly said: “For many decades we have studied how a range of hormones act on the brain to regulate appetite and body weight.

“Many of the insights that we have gained through our previous research in obesity are likely to be highly relevant to cancer cachexia, a condition where hormonal and metabolic changes secondary to cancer impact on the brain to reduce, rather than increase appetite.

“We have recently discovered a pathway in the brain which is key to controlling whether we put food calories in excess of our basic needs into fat or into muscle.  This pathway is likely to be highly relevant to patients with cancer cachexia who are particularly affected by a loss of muscle.”  

Dr Giulia Biffi’s research focuses on understanding the biology of the tumour microenvironment in pancreatic cancer with the aim of developing new treatments and diagnostics.

Dr Biffi, who co-leads the CRUK Cambridge Centre Pancreatic Cancer Programme, said: “Cachexia is predominant in pancreatic cancer patients; it increases patient mortality and can prevent patients accessing treatment as they are too weak. If we can identify ways to treat cachexia more people could be treated for their cancer.

“This is a fantastic opportunity to interact with a highly multi-disciplinary team to bring our different scientific and clinical strategies towards a single common goal.”

• Dr Coll with Dr Claire Connell have recently opened a clinical study at Addenbrooke’s hospital which aims to understand the mechanisms underlying weight loss in cancer patients by investigating changes to metabolism and the immune system. They hope the findings from the Metabolic and Immunological Phenotyping in Patients with Cancer (MIPPaC) study will guide future research and help to design treatments that can alleviate or prevent weight loss and improve outcomes for cancer patients.