GoKawiilIn laboratories and hospitals around the world, a new generation of cancer researchers is working on the treatments and technologies of tomorrow. Some have turned their focus to improving imaging techniques for diagnostics; others are developing minimally invasive tests for early detection. Despite the differences in their work, they are united in achieving a common goal — better survival rates for people with cancer.
AYESHA NOORANI: Genome pattern sleuth
Ayesha Noorani maps DNA mutation patterns to learn how cancer develops over time.Credit: Paddy Mills
As a medical student at the University of Cambridge, UK, Ayesha Noorani planned to pursue a career as a vascular surgeon. But when an uncle back home in Karachi, Pakistan, died of oesophageal cancer in his early 50s, she chose a different path. “I was struck by how little we could do for my uncle, and how little was known about the disease,” she says. Now a clinician scientist at the Wellcome Sanger Institute in Cambridge, Noorani studies two of the most aggressive cancers — gastric and oesophageal — which arise in closely connected organs and share many of the same risk factors and treatment paths.
Many biological processes can increase a person’s risk of developing cancer, such as cumulative damage from ageing, chronic inflammation or certain defects in DNA repair. Noorani wants to understand the genetic factors that determine why these risks lead to some people developing cancer while others remain unaffected by the disease. The key, she says, is finding specific genetic signatures in a patient’s genome and monitoring them over time. “I’m very much interested in the evolution of cancer — the fact that it’s dynamic and changes with time,” says Noorani.
Working with patients at high risk of oesophageal cancer allows Noorani to map genetic changes in oesophageal cells before cancer develops and explore how those changes might contribute to the disease. Two conditions that are particularly important for this work are achalasia — a swallowing disorder that limits food and drink from moving down the oesophagus into the stomach — and Chagas disease — a parasitic illness that can cause heart failure and digestive complications — because they are linked to an increased risk of oesophageal cancer.
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Discovering genetic signatures and how they affect risk in healthy people could be a “game-changer”, says Noorani. Detection before symptoms appear is crucial, she adds, because oesophago-gastric cancer is increasingly affecting people in their 30s and 40s.
Noorani is also investigating how oesophageal adenocarcinoma, a common type of oesophageal cancer that originates in gland-forming cells, develops over time. In a 2020 study1, she and her colleagues compared the genetic profile of tissue samples collected from the primary tumour and metastatic sites in patients with oesophageal adenocarcinoma during treatment and shortly after death. This allowed them to trace the cancer’s evolution “in a very detailed way”, Noorani says.
The team found that rather than spreading in a stepwise manner through the lymph nodes as previously assumed, the cancer seemed to disperse quickly from the original tumour to multiple sites. “This was a new model of metastasis,” Noorani says. The findings support the modern approach to chemotherapy, which extends treatment after surgery to remove residual metastatic cells that could fuel further spread.
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