New discovery paves way for targeted treatment for oesophageal cancer

A new discovery that oesophageal cancer can be classified into three different subtypes paves the way for targeted treatments that can be tailored to the individual type of the disease.

Scientists funded by Cancer Research UK and the Medical Research Council, looked at the complete genetic make-up of 129 cancers of the oesophagus and were able to subdivide the disease into three distinct types based on patterns detected in the DNA of the cancer cells, called signatures. This discovery could help find drugs that target specific weaknesses in each subtype of the disease, which could make treatment more effective and boost survival.

The first subtype they found had faults in their DNA repair pathways. Damage to this pathway is known to increase the risk of breast, ovarian and prostate cancers. Patients with this subtype may benefit from a new family of drugs called PARP inhibitors that kill cancer cells by exploiting this weakness in their ability to repair DNA.

The second subtype had a higher number of DNA mistakes and more immune cells in the tumours, which suggests these patients could benefit from immunotherapy drugs already showing great promise in a number of cancer types such as skin cancer.

The final subtype had a DNA signature that is mainly associated with the cell ageing process and means this group might benefit from drugs targeting proteins on the surface of the cancer cells, which make cells divide.

Tailored treatment for individual patients

Professor Rebecca Fitzgerald, lead researcher based at the MRC Cancer Unit at the University of Cambridge, said: “Our study suggests we could make changes to the way we treat oesophageal cancer. Targeted treatments for the disease have so far not been successful, and this is mostly down to the lack of ways to determine which patients might benefit from different treatments. These new findings give us a greater understanding of the DNA signatures that underpin different subtypes of the disease and means we could better tailor treatment.

“The next step is to test this approach in a clinical trial. The trial would use a DNA test to categorise patients into one of the three groups to determine the best treatments for each group and move away from a one-size-fits-all approach.”

Each year around 8,800 people are diagnosed with oesophageal cancer in the UK and just 12 per cent survive their disease for at least 10 years. Cancer Research UK has made research into oesophageal cancer a priority.

Professor Peter Johnson, Cancer Research UK’s chief clinician, said: “Being able to distinguish distinct types of oesophageal cancer is a genuinely new discovery from this work. For the first time we may be able to identify and test targeted treatments designed to exploit the cancer’s specific weaknesses. Although survival rates from oesophageal cancer have been slowly rising in the last few years they are still far too low, and this research points the way to a completely new way of understanding and tackling the disease.”

The study is part of the Cancer Research UK funded International Cancer Genome Consortium and is published in Nature Genetics.

Abnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. Full medical glossary
The basic unit of all living organisms. Full medical glossary
The building blocks of the genes in almost all living organisms - spelt out in full as deoxyribonucleic acid. Full medical glossary
The basic unit of genetic material carried on chromosomes. Full medical glossary
Relating to the genes, the basic units of genetic material. Full medical glossary
A treatment that modifies the immune response for the prevention or treatment of disease. Full medical glossary
The gullet, the part of the gastrointestinal system that extends down from the mouth cavity to the stomach. Full medical glossary
relating to the ovaries Full medical glossary
A gland that surrounds the urethra near the bladder. It produces a fluid that forms part of the semen. Full medical glossary
Compounds that form the structure of muscles and other tissues in the body, as well as comprising enzymes and hormones. Full medical glossary
A group within a group. Full medical glossary
An abnormal swelling. Full medical glossary