Opting for a more personalised approach to fighting cancer

EU-funded researchers are developing innovative tools and 'liquid biopsy' techniques to improve the diagnosis and treatment of cancer by targeting the detached tumour cells that cause the vast majority of deaths. Once validated and commercialised, their approach promises to lead to more effective and personalised care for cancer patients Breast cancer, the most common form of cancer among women worldwide, is a prime example of the many types of the disease that could be treated more effectively with an emerging diagnostic approach being advanced by researchers working in the EU-funded CTCTRAP and CAREMORE projects. Breast tumours, because of their location, are usually found relatively early in their formation, but breast cancer still accounts for more than 500,000 deaths worldwide each year. In 99 per cent of cases, death occurs not as a result of the primary tumour but because of tumour metastasis – when cells detach from the primary tumour and form new malignancies elsewhere, such as the liver or lungs, for example. “The primary tumour is usually biopsied and removed early, the type of cancer cells is identified and this characterisation is traditionally used to define the course of treatment,” explains Professor Leon Terstappen at the University of Twente in the Netherlands, co-ordinator of the CTCTRAP project. “However, the metastatic tumours may differ substantially from the primary tumour, and the chosen course of treatment may therefore prove to be ineffective.”

‘Real-time liquid biopsy’ for optimised cancer therapy

Performing a traditional biopsy to extract tissue samples from metastatic tumours often carries significant risks and discomfort for patients, but an emerging approach is helping to overcome the problem. Diagnostic techniques based on the identification of circulating tumour cells (CTC) in the blood have been likened to performing a 'liquid biopsy'. Blood is drawn from the patient and advanced diagnostic tools are used to detect and characterise minute amounts of circulating tumour cells in the blood samples. This enables metastasis to be detected sooner and more accurately, patients to be monitored more closely and treatments to be chosen in a more targeted and personalised manner. Terstappen was responsible for the development of CellSearch, the only CTC enumeration technology cleared for use in the US by that country’s drugs regulator and which won the highly prestigious Prix Galien award in 2009 for advancing pharmaceutical research. However, even with that technology, detecting CTCs in blood is difficult given their extremely low prevalence in most patients. In response, Terstappen and other researchers at universities, research institutes and small businesses are working together in the CTCTRAP project to develop more advanced tools and techniques to collect and examine CTCs. Their key innovation is to use apheresis as a way to collect tumour cells from peripheral blood in cancer patients – an approach they plan to validate in clinical trials. Apheresis involves drawing litres of blood from a patient and separating it into its constituent components. The CTCs are then captured in real time and the blood devoid of tumour cells is re-infused back into the patient. “Using this method, we hope to obtain CTC samples in all patients at risk for recurrence or diagnosed with metastatic disease,” says Terstappen. “The molecular characterisation of these CTCs is expected to generate new knowledge on the mechanism of metastasis, provide improved risk assessment and help optimise the therapy choices for cancer patients. If CTC apheresis is successful, we are confident that it will lead to a radical change in the diagnosis and treatment of solid tumours.” CTCTRAP’s first studies will focus on breast and prostate cancer. Meanwhile, researchers working in the CAREMORE project are applying CTC technology specifically to the diagnosis and treatment of breast cancer.

Improving therapy choice, too

The CAREMORE consortium is developing novel CTC-based diagnostic tests and plans to validate them in a clinical setting with the aim of improving therapy choices for patients with metastatic breast cancer. Their tools will look at the presence of two proteins – oestrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) – that are essential in deciding the optimal course of cancer treatment. However, instead of identifying the proteins from the primary tumour, the CAREMORE team will develop innovative tools to do so from circulating tumour cells, explains Erika Assarsson, head of research at CAREMORE co-ordinating partner Olink in Sweden. “The presence of these proteins, which act as therapy targets as well, is usually assessed on primary tumour tissue in standard daily practice,” she says. “However, only specific clones within the primary tumour may have the ability to metastasise. As a result, there is up to a 40 per cent discrepancy between the expression of HER2 and ER when comparing primary tumours with their corresponding metastases. By identifying the proteins in CTCs we expect to more accurately characterise the metastases and enable the application of more targeted and effective treatment options.” Both CAREMORE and CTCTRAP, which include several small businesses among their respective consortiums, plan to commercialise the tools they are developing after they have been validated in the projects – potentially greatly enhancing the fight against cancer worldwide.

Project details

Project acronym: CAREMORE
Participants: Sweden (Co-ordinator), Denmark, Netherlands
Project Reference: N° 601760
Total cost: €7,389,897
EU contribution: €5,127,632
Duration: September 2013-August 2016

Project acronym: CTCTRAP
Participants: Netherlands (Co-ordinator), Germany, France, UK, Hungary, Italy, Estonia
Project Reference: N° 305341
Total cost: €8,321,935
EU contribution: €6,000,000
Duration: September 2012-August 2016