Almost 500,000 new cases of oesophageal cancer are diagnosed worldwide every year. However, diagnosis usually only occurs at an advanced stage, and survival over 5 years is less than 15%. As this type of cancer does not form a tumour-like growth, but instead remains flat in appearance, it is extremely difficult to detect early with conventional screening methods.
In a recent study published in Science Translational Medicine, a team of researchers and physicians developed a new technique for oesophageal cancer detection using a fluorescently-labelled molecule that sticks to pre-malignant cells developed as a consequence of Barrett's oesophagus. This condition, which is usually caused by long-term acid reflux from the stomach, is characterised by abnormal (but not cancerous) cells lining the oesophagus. These cells have an increased risk of turning malignant in time.
"The need for this technique exists because this cancer is a deadly disease, growing faster than any other cancer in Westernized countries", says Dr Thomas Wang, gastroenterologist from the University of Michigan, USA, and leading author in the study. The research team identified a small molecule called peptide that binds strongly to early stage cancerous cells. The peptide was then labeled with a fluorescent tag, allowing the visualization of cells that have undergone changes.
The researchers tested many compounds, but peptides were the preferred option, explains Dr Wang, mainly due to their safety. After all, "they are natural fragments of proteins that we ingest as part of our daily meals", he adds. They are also quick and easy to use, highly specific and relatively cheap to produce, making this a very attractive method for routine use in the future.
To carry out clinical studies, "we had to overcome the usual regulatory hurdles", says Dr Wang, but "after all the toxicology and pharmacology studies were accepted, an Investigational New Drug application was approved by the US Food and Drug Administration (FDA) to perform the first-in-humans study". Twenty-five patients scheduled for routine surveillance were enrolled and had an endoscopy after application of the peptide. Tissue analysis confirmed the accurate detection of diseased cells using this method, demonstrating the potential to perform non-invasive "intelligent biopsies".
At this stage, the method's main limitation is its inability to detect changes located deep underneath the surface, and important lesions can still be missed. To overcome this obstacle, the team is currently hard at work, developing an imaging approach able to detect deeper into tissues.
Nevertheless, when asked about potential applications, Dr Wang has a positive outlook. "In the future, this strategy can be used to improve diagnosis, intervention and management of most cancers of epithelial origin that are challenged by flat morphology, heterogeneity and patchy distribution. These include bladder, cervix, colon, oropharynx, lung, pancreas, and stomach, which in total comprise >80% of all deaths by cancer in the US".