Using cancer to find tumours
Small molecules that bind to tumour cells circulating in the blood could catch cancer sooner
Sun, D. et al.: "Aptamer-based electrochemical cytosensors for tumor cell detection in cancer diagnosis: A review," Analytica Chimica Acta (2019)
Some of the most dangerous cancer cells could be repurposed to diagnose cancer quickly and get effective treatment underway.
Researchers worldwide are seeking methods to detect the cells that are shed from a primary tumour and which then circulate in the bloodstream. These circulating tumour cells (CTCs) can create dangerous metastases – the secondary tumours in sensitive sites such as the brain and bone. But their presence in the blood also makes them accessible to tests that can detect them.
One of the most promising approaches is to use small molecules that will bind specifically to tumour cells and then act as flags that signal the cancer cells’ presence. Such molecules are generally known as aptamers. Their use in cancer diagnosis is reviewed in Analytica Chimica Acta by Duanping Sun and colleagues at Guangdong Pharmaceutical University and Sun Yat-Sen University in Guangzhou, China.
In addition to diagnosis, the procedures may also help to monitor the effectiveness of therapy and refine treatments to achieve a better response.
The review focuses on CTC-detection methods that use electrochemistry – the ability of chemicals to generate electrical signals that can be picked up by monitoring equipment.
“Aptamer-based electrochemical cytosensors have attracted particular attention due to their merits of rapid response, easy operation, affordability and nondestructive analysis,” Sun explains. The aptamers discussed in the review are mainly small nucleic acid molecules, such as DNA and RNA.
Sun’s own research group has developed a method that can detect cells from human liver cancers at a level as low as five cells per millilitre of blood.
Different small molecule aptamers can be highly selective in their ability to bind to different types of tumour cells. This finely-tuned specificity is a key advantage of aptamer-based sensing. The binding of aptamers to their target cells, however, must generally be amplified in some way in order to generate a detectable electrochemical signal. Sun’s own method, for example, uses a combination of a small DNA molecule with catalytic properties (a ‘DNA-zyme’) and a protein enzyme to amplify the initial molecular interaction into an identifiable signal.
The authors review a wide variety of electrochemical techniques that generate output signals ranging from simple voltage or resistance changes to complex photo-electrochemistry that generates output as light.
Sun reports that a key challenge for the emerging field is the molecular variability of cancer cells. Although this can allow different types of cells to be distinguished, it also introduces significant barriers to ensuring that all cells of interest can be detected.
Another challenge for the future is to incorporate the electrochemical procedures into integrated microfluidic devices, allowing a small sample of blood to flow through tiny channels and generate meaningful signals quickly and effectively.
These challenges are reflected in the fact that at present only one CTC-detection device has obtained clearance from the US Food and Drug Administration for use in clinical practice.
“Nevertheless, we do hope and believe new CTC-detecting devices will make a significant contribution to the fight against cancer in the future,” Sun concludes.
For further information about the article, please contact Duanping Sun on WeChat: DuanpingSun or 13622869694.