Spotlight: our work in oesophageal cancer

27 April 2022
Oseophageal cancer piece

The world’s 7th most common malignancy, oesophageal cancer results in more than 500,000 deaths globally each year. For Oesophageal Cancer Awareness Month, we’re shining a light on much-needed research into the disease, with a collection of stories from our research community.

  1. Unravelling the role of chronic inflammation in oesophageal cancer

Despite chronic inflammation being linked to an astounding 25% of cancers around the world, we still know very little about how it drives the development of the disease. In answering our Cancer Causes challenge, one team is exploring the connection between chronic inflammation and 4 types of cancer, including oesophageal adenocarcinoma.

The team aims to solve this longstanding mystery by focusing on how inflammation affects the stroma – the connective tissue that surrounds organs – which evolves throughout the course of inflammation, providing increasingly fertile ground for tumorigenesis. Particularly, they want to understand whether reprogramming of the stroma could prevent, slow or even revert the cascade of the chronically inflamed oesophagus to malignancy. “Inflammation-associated cancers are among the most lethal cancer types in the world,” says team lead Thea Tlsty. “This is what keeps me up at night and why I’m so excited by the opportunity we have with Cancer Grand Challenges.” 

Read more about the team’s aims in this article from Thea and postdoctoral researcher Elee Shimshoni.

  1. Understanding the huge global variation in oesophageal cancer incidence

The team taking on our Unusual Mutation Patterns challenge set out to understand why the incidence of oesophageal squamous cell carcinoma (ESCC) – the most common form of oesophageal cancer – varies so dramatically around the world and is more than 100x more common in some countries than others. But instead of finding a signature of DNA damage that may link the phenomenon to an unknown carcinogen in regions of high incidence, the team found that no mutational signature exists to explain the profound difference in ESCC rates across the world.

“As is often the case in research, we set off asking one question but ended up with many new ones,” says Sarah Moody, postdoctoral researcher on the team taking on our Unusual Mutation Patterns challenge.

Read more from Sarah and watch team lead Mike Stratton discuss the findings in this explainer video.

  1. Identifying a new route to tumour evolution

Additionally, the Unusual Mutation Patterns team showed that 90% of ESCC samples from around the world carry mutational signatures associated with the activity of APOBEC – a family of enzymes that are usually responsible for protecting cells against viral infection.

Earlier this year, members of the team built on these findings by linking APOBEC to tumour evolution, via the repeated hypermutation of extrachromosomal DNA. A deeper understanding of this connection could lead to new therapeutic interventions to avoid tumour evolution in people whose cancers are driven by APOBEC.

“It’s fascinating to think we’ve found this completely novel route to tumour evolution,” says co-investigator Ludmil Alexandrov. Learn more here.

Learn more about oesophageal cancer, including its symptoms and risks.

Image credit: Wikimedia Commons

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