Large genetic analysis of oesophageal cancer could lead to better clinical trials

The two main types of oesophageal, or food pipe cancer, display distinct genetic characteristics and should be studied separately in clinical trials, according to a large US study. 

The analysis from The Cancer Genome Atlas (TCGA) Research Network calls into question the classification of the disease. 

Experts believe the study could have implications for the design of future clinical studies, serving as a “reference manual” for those running clinical trials and developing new drugs, said lead researcher Dr Adam Bass from the Dana-Farber Cancer Institute in the US. 

Tumours are commonly classified based on how the cancer cells look under the microscope and where the cases occur in the world.

Oesophageal cancer has long been split into two main categories: adenocarcinomas, which look like stomach or bowel cancers; and squamous cell carcinomas, which are similar to some lung, skin, and head and neck cancers. 

But little has been known about how these cancers differ at the molecular, or genetic level. 

To find out more, the researchers used publicly available data from TCGA – a collaborative effort to understand more about the genetics of cancer – to study 559 oesophageal and stomach cancer samples. 

Published in the journal Nature, the study found that oesophageal adenocarcinomas and squamous cell carcinomas are genetically distinct. They also found that cancers occurring in the upper region of the oesophagus display molecular similarities to cancers of the head and neck, while those further down the food pipe closely resemble a type of stomach cancer.

The research team argues that because of these findings, clinical trials should group oesophageal cancer patients based on their molecular sub-type, something which Professor Rebecca Fitzgerald, a Cancer Research UK expert in oesophageal cancer, agrees with.

“This is the most comprehensive genetic analysis of oesophageal cancer to date,” she said. “And it provides more detail on the molecular characteristics of the different types of the disease than was previously available. 

“The finding that the two main types of oesophageal cancer – squamous cell and adenocarcinoma – are distinct is not surprising, and is supported by other studies. 

“But this study makes it clear that patients with these different types of oesophageal cancer shouldn’t be put in the same arm of clinical trials.

“This is something that many of us have been suggesting for a long time. So this latest study should help doctors ensure that these subgroups are separated in future trials.”