Stomach cancer ‘fingerprint’ may offer clues for targeted treatment
The pattern of mutations, one of twenty initially discovered two years ago by UK researchers, predicts that cancers bearing the signature should be vulnerable to certain drugs.
"Research like this is showing ever more clearly that even single ‘types’ of cancer are actually different diseases" - Professor Charlie Swanton, Cancer Research UK
Although trials are needed to confirm the findings, the discovery of a link between the signature and stomach cancer could be another step towards a more personalised era of treatment.
The nature of the defects – referred to as signature 3 – suggest that cancer cells’ ability to repair damage to their DNA is impaired.
Because of this, they could be more susceptible to the effects of platinum drugs, which attack and eventually break the DNA, and newer drugs called and PARP inhibitors, which target cells with faulty DNA repair systems.
This idea was given credence earlier this year, when found signs that patients whose pancreatic cancers carried signature 3 were more likey to have responded to platinum drugs.
Stomach (or gastric) cancer is the third leading cause of cancer death in the world, and often responds poorly to existing treatments.
Research last year showed that the disease existed in four different subtypes.
So an international team of researchers, led by scientists at the Wellcome Trust Sanger Institute, set about trying to ascertain if the fingerprint, known as ‘signature 3’ is ever present in this, and other cancers.
The large-scale computer-based study searched for signature 3 in a database of cancer DNA from 10,250 patients who had been diagnosed with 36 different types of tumours.
Published in Nature Communications, the results confirmed the molecular pattern in a subset of around 10 per cent of stomach cancers.
This compared to 30 per cent of ovarian, 27 per cent of breast and eight per cent of pancreatic cancers – diseases for which this study also provides useful results.
In breast cancer, for example, it could eventually prompt clinicians to look further than for faults in the BRCA1 and BRCA2 genes (both involved in DNA repair), and prevent them missing many cases in patients solely carrying signature 3.
Study leader Dr Ludmil Alexandrov, from the Los Alamos National Laboratory in the USA, said: “Not only did we confirm the presence of signature 3 in a significant percentage of breast, ovarian, and pancreatic cancers, we also found this molecular fingerprint in approximately 10 per cent of stomach cancers.,"
“This subset of stomach cancer is likely to have a defective DNA break-repair mechanism, and could therefore be susceptible to existing treatments such as platinum drugs or PARP inhibitor drugs."
Professor Charlie Swanton, a Cancer Research UK-funded expert in cancer genetics at the Francis Crick Institute, said: “Research like this is showing ever more clearly that even single ‘types’ of cancer are actually different diseases, needing different treatments.
"In this case, the researchers predict that there’s a subtype of stomach cancer which should theoretically respond well to drugs used for other cancers.”
It could also help decipher who would be most likely to benefit from platinum drugs, which are already used as a treatment for gastric cancer, he said.
“But we still need formal proof that patients whose stomach cancers carry such genetic fingerprints would actually benefit from these drugs – and that means careful, robustly designed trials aimed at answering this question.
“We’re moving towards a more personalised era of treatment, but there’s still a way to go before we get there,” Professor Swanton added.
- Image via Wikimedia Commons