Genetic chaos in tumours could help predict chemo response
Francis Crick Institute and UCL Cancer Institute scientists, funded by Cancer Research UK, the Academy of Medical Sciences and the National Institute for Health Research, have shown how the level of genetic chaos in tumours could help predict patients’ response to chemotherapy according to research published in Cancer Discovery.
"Studies like this are edging us closer to being able to predict cancer’s ‘next move’, hopefully leading to sophisticated new treatment combinations that will outsmart the disease before it can really take hold." - Professor Charles Swanton
The scientists analysed several tumour samples taken from eight different oesophageal cancer patients before and after chemotherapy. For each tumour, they assessed whether particular genetic faults were present in all the samples from each patient, or in only a proportion of them.
They found that most tumours were made up of a patchwork of faults. The more complicated this patchwork and the greater the genetic differences within each tumour, the more aggressive the tumour and the less likely it was to respond well to cisplatin – a drug commonly used to treat oesophageal cancer.
Importantly, the cells within these more aggressive tumours were also prone to picking up additional faults following cisplatin exposure, suggesting that the chemotherapy itself was driving new mutations and genetic chaos in drug resistant tumours.
This knowledge could one day be used to identify groups of patients with more aggressive tumours that would benefit from different approaches, such as earlier surgery or combinations of ‘smart drugs’ that target specific faulty molecules within tumours.
Study leader Professor Charles Swanton from the UCL Cancer Institute and Francis Crick Institute, said: “Studies like this are edging us closer to being able to predict cancer’s ‘next move’, hopefully leading to sophisticated new treatment combinations that will outsmart the disease before it can really take hold. This will be particularly crucial for hard-to-treat cancers like oesophageal cancer, which has seen disappointingly little improvement in survival in recent decades.”
Dr Kat Arney, Cancer Research UK’s science information manager, said: “Oesophageal cancer claims nearly 8,000 lives every year and more than half of all patients die within twelve months of diagnosis, so we’re urgently investing in more research to understand the disease, detect it earlier and treat it more effectively. By understanding the genetic chaos that lies at the heart of these tumours, we hope to make a real difference to this stark statistic and keep many more families together for longer.”
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Murugaesu N. et al, Tracking the genomic evolution of esophageal adenocarcinoma through neoadjuvant chemotherapy, Cancer Discovery (2015).