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Study opens door to targeted treatments for esophageal cancer

September 5, 2016
Cancer Research UK
Esophageal cancer can be classified into three different subtypes, paving the way for testing targeted treatments tailored to patients' disease for the first time, scientists have discovered.

Scientists have discovered that esophageal cancer can be classified into three different subtypes, paving the way for testing targeted treatments tailored to patients' disease for the first time.

This discovery, published in Nature Genetics, could help find drugs that target specific weaknesses in each subtype of the disease, which could make treatment more effective and boost survival.

The scientists, funded by Cancer Research UK and the Medical Research Council, looked at the complete genetic make-up of 129 esophageal cancers and were able to subdivide the disease into three distinct types based on patterns detected in the DNA of the cancer cells called signatures.

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 aging process and means this group might benefit from drugs targeting proteins on the surface of the cancer cells which make cells divide.

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 esophageal 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 esophageal cancer in the UK and just 12 per cent survive their disease for at least 10 years. Cancer Research UK has prioritised research into esophageal cancer to help more people survive the disease by bringing people together, building infrastructure and developing the next generation of research leaders.

Professor Peter Johnson, Cancer Research UK's chief clinician, said: "Being able to distinguish distinct types of esophageal 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 esophageal 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."

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Materials provided by Cancer Research UK. Note: Content may be edited for style and length.

Journal Reference:

  1. Maria Secrier, Xiaodun Li, Nadeera de Silva, Matthew D Eldridge, Gianmarco Contino, Jan Bornschein, Shona MacRae, Nicola Grehan, Maria O'Donovan, Ahmad Miremadi, Tsun-Po Yang, Lawrence Bower, Hamza Chettouh, Jason Crawte, Núria Galeano-Dalmau, Anna Grabowska, John Saunders, Tim Underwood, Nicola Waddell, Andrew P Barbour, Barbara Nutzinger, Achilleas Achilleos, Paul A W Edwards, Andy G Lynch, Simon Tavaré, Rebecca C Fitzgerald, Ayesha Noorani, Rachael Fels Elliott, Jamie Weaver, Caryn Ross-Innes, Laura Smith, Zarah Abdullahi, Rachel de la Rue, Alison Cluroe, Shalini Malhotra, Richard Hardwick, Hugo Ford, Mike L Smith, Jim Davies, Richard Turkington, Stephen J Hayes, Yeng Ang, Shaun R Preston, Sarah Oakes, Izhar Bagwan, Vicki Save, Richard J E Skipworth, Ted R Hupp, J Robert O'Neill, Olga Tucker, Philippe Taniere, Fergus Noble, Jack Owsley, Laurence Lovat, Rehan Haidry, Victor Eneh, Charles Crichton, Hugh Barr, Neil Shepherd, Oliver Old, Jesper Lagergren, James Gossage, Andrew Davies, Fuju Chang, Janine Zylstra, Grant Sanders, Richard Berrisford, Catherine Harden, David Bunting, Mike Lewis, Ed Cheong, Bhaskar Kumar, Simon L Parsons, Irshad Soomro, Philip Kaye, Pamela Collier, Laszlo Igali, Ian Welch, Michael Scott, Shamila Sothi, Sari Suortamo, Suzy Lishman, Duncan Beardsmore, Hayley E Francies, Mathew J Garnett, John V Pearson, Katia Nones, Ann-Marie Patch, Sean M Grimmond. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance. Nature Genetics, 2016; DOI: 10.1038/ng.3659

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Cancer Research UK. "Study opens door to targeted treatments for esophageal cancer." ScienceDaily. ScienceDaily, 5 September 2016. <>.
Cancer Research UK. (2016, September 5). Study opens door to targeted treatments for esophageal cancer. ScienceDaily. Retrieved May 29, 2017 from
Cancer Research UK. "Study opens door to targeted treatments for esophageal cancer." ScienceDaily. (accessed May 29, 2017).