Classifying Esophageal Cancer into Subtypes May Lead to Better, More Tailored Treatments

Classifying Esophageal Cancer into Subtypes May Lead to Better, More Tailored Treatments

A study found that esophageal cancer can be distinguished between three subtypes, which paves the way for testing new tailored treatment approaches to fit individual patients’ needs.

The study, “Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance,” published in Nature Geneticsmay help researchers develop new drugs that target the specific weaknesses of each subtype, potentially increasing survival rates by making treatment more effective.

“Being able to distinguish distinct types of esophageal cancer is a genuinely new discovery from this work,” Prof. Peter Johnson, chief clinician at Cancer Research UK, said in a press release. “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.”

It’s estimated that 8,800 people are diagnosed with esophageal cancer every year in the United Kingdom. Survival rates past 10 years for this type of cancer are particularly low. Cancer Research UK has prioritized research into esophageal cancer to help boost survival rates and help find new treatments.

A scientific team led by Prof. Rebecca Fitzgerald and based at the MRC Cancer Unit at the University of Cambridge received funding from Cancer Research UK and the Medical Research Council to look at the full genetic makeup of 129 esophageal cancers. With this study, they were able to divide the disease into three subtypes based on their “signatures” (patterns detected in the DNA of the cancer cells).

  • Subtype 1 – esophageal cancer with weaknesses in the DNA repair pathways. Damage to this pathway is known to increase risks of developing other cancers, like breast or prostate. Researchers believe patients who have this subtype of the disease may benefit from a novel class of drugs called PARP inhibitors, which eliminate cancer cells by exploiting their inability to repair DNA.
  • Subtype 2 – esophageal cancer with a high number of DNA mistakes and more immune cells in the tumors. This suggests that patients with this subtype may benefit from immuno-oncology therapies already under trial for different types of cancer.
  • Subtype 3 – esophageal cancer with a DNA signature that is mostly linked to cell aging processes. Researchers believe these patients may benefit from drugs targeting proteins on the surface of cancer cells that are involved in cell proliferation.

“Our study suggests we could make changes to the way we treat esophageal cancer,” Fitzgerald said. “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,” she added. “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.”

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