International genomics research led by the University of Leicester has used artificial intelligence (AI) to study an aggressive form of cancer, which could improve patient outcomes.
Mesothelioma is caused by breathing asbestos particles and most commonly occurs in the linings of the lungs or abdomen. Currently, only seven per cent of people survive five years after diagnosis, with a prognosis averaging 12 to 18 months.
New research undertaken by the Leicester Mesothelioma Research Program has now revealed, using AI analysis of DNA-sequenced mesotheliomas, that they evolve along similar or repeated paths between individuals. These paths predict the aggressiveness and possible therapy of this otherwise incurable cancer.
Professor Dean Fennell, Chair of Thoracic Medical Oncology at the University of Leicester and Director of the Leicester Mesothelioma Research Programme, said: "It has long been appreciated that asbestos causes mesothelioma, however how this occurs remains a mystery.
"Using AI to interrogate genomic 'big data', this initial work shows us that mesotheliomas follow ordered paths of mutations during development, and that these so-called trajectories predict not only how long a patient may survive, but also how to better treat the cancer -- something Leicester aims to lead on internationally through clinical trial initiatives."
While use of asbestos is now outlawed -- and stringent regulations in place on its removal -- each year around 25 people are diagnosed with mesothelioma in Leicestershire and 190 are diagnosed in the East Midlands. Cases of mesothelioma in the UK have increased by 61% since the early 1990s.
Until very recently, chemotherapy was the only licensed choice for patients with mesothelioma. However, treatment options start to become limited once people stop responding to their treatment.
Professor Fennell in collaboration with the University of Southampton recently made a major breakthrough in treating the disease by demonstrating that use of an immunotherapy drug called nivolumab increased survival and stabilized the disease for patients. This was the first-ever trial to demonstrate improved survival in patients with relapsed mesothelioma.
Illustration: Genomic intratumour heterogeneity in MPM. Pleural mesothelioma tissue sampling locations were consistent between patients involving the apex (region1, R1), the pericardium (R2), anterior costophrenic angle (R3), posterior costophrenic angle (R4) and the oblique fissure (R5). The rationale for selecting the anatomically stereotyped sites at the time of tissue sampling was to ensure maximum coverage of the tumor from superior to inferior; medial to lateral; and anterior to posterior. We chose the oblique fissure (R5) as this is common to both the right and left lung and could be a reliable anatomical site bilaterally. Spatial evolution of mesothelioma would be expected to be best reflected in samples at maximum distance from one another, reflecting the inherent intratumor heterogeneity. These regions are represented by the most superior region (R1) and the inferior (R3 and R4).
Nature Communications, 2021; 12 (1).
Read more...
University of Leicester News Release (03/26/21)
Science Daily (03/26/21)
Abstract (Nature Communications, 2021; 12 (1).)