US scientists analysing tumour samples from patients with mesothelioma – a form of cancer linked with asbestos exposure – have mapped out the gene faults associated with the disease in unprecedented detail.
The findings, by researchers at the Brigham and Women’s Hospital in Boston working with colleagues at pharmaceutical company Genentech, suggest some patients may respond to existing experimental drugs.
An expert from Cancer Research UK said the discovery, based on samples from more than 200 patients, were the most detailed analysis to date.
“Mesothelioma is a cancer for which we’re urgently searching for new treatments, and this study provides us with a map of how to find them,” said Professor Dean Fennell, a Cancer Research UK-funded expert in mesothelioma from the University of Leicester.
“It’s the most comprehensive analysis to date of the gene defects in mesothelioma cells, and confirms what previous, smaller studies have shown. Most notably it confirms the importance of several genetic flaws, suggesting that some patients could do well on a number of experimental drugs being tested for other cancers – this will now need testing in clinical trials.”
The researchers compared genetic data from normal and cancerous tissues from 201 patients’ tumour samples, unearthing more than 2,500 faults, and 10 genes commonly altered genes.
“By studying so many samples, we’ve been able to describe a spectrum of mutations for this rare disease. A small number of these mutations have been found previously in other cancers, and drugs have been developed to target these mutations,” said study leader Dr Raphael Bueno.
“This new work suggests that patients with such mutations may benefit from certain existing drugs.”
Two patients appeared to have mutations that suggested they might have responded to a leukaemia drug called imatinbib, which targets a gene defect called BCR-Abl. Others had tumours that produced high levels of a molecule called PD-L1, thought to confer sensitivity to new immunotherapy drugs.
“We plan to continue this important research through investigator-sponsored trials evaluating the potential use of cancer immunotherapies for the treatment of mesothelioma,” said Bueno.
The research also identified hallmarks of several processes at play inside cancer cells as the disease developed. But what was still missing, said Professor Fennell, was detailed information about how asbestos triggered mesothelioma.
“What’s still not clear is the identity of the key gene faults responsible for mesothelioma’s initiation. Finding this out will be key to understanding how to beat this terrible disease. So we still need to dig deeper into the genetics and work out how to exploit what we find – something several research teams, including my own, are working on.”
- “Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations,” Nature Genetics (2016). DOI: 10.1038/ng.3520