Researchers say they 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.

Their study (“Mutational Signatures in Esophageal Adenocarcinoma Reveal Etiologically Distinct Subgroups with Therapeutic Relevance”), published in Nature Geneticscould help find drugs that target specific weaknesses in each subtype of the disease, which could make treatment more effective and boost survival, according to the investigators.

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

The first subtype they found had faults in 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 poly(ADP-ribose) polymerase (PARP) inhibitors that kill cancer cells by exploiting this weakness in their ability to repair DNA.

The second subtype had a higher number of mutations and more immune cells in the tumors, 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 that make cells divide.

“Our study suggests we could make changes to the way we treat esophageal cancer,” said Rebecca Fitzgerald, M.D., lead researcher based at the MRC Cancer Unit at the University of Cambridge. “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 categorize 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.”.

According to Peter Johnson, M.D., Cancer Research UK's chief clinician, “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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