CANCER-ID

Today, many cancer patients have to undergo biopsy surgery to provide doctors with the cell samples they need to diagnose the disease, determine the treatment needed, and then monitor how well a treatment is working. ###Needless to say, doctors cannot carry out biopsies too often because they are invasive, costly, and risky to the patient. Yet cancer is a dynamic disease and patients would benefit immensely from more regular analyses of their condition.

Cancerous tumours shed cells and fragments of DNA into the bloodstream, and IMI’s CANCER-ID project has developed and validated a range of methods and protocols to detect these ‘circulating tumour cells’ (CTCs) and DNA and analyse them – a so-called ‘liquid biopsy’.

According to project coordinator Dr Thomas Schlange of Bayer, the results revealed that the protocols need to be adapted to different clinical settings – there is no ‘one size fits all’ solution. ‘CANCER-ID helped a lot to raise awareness of the necessity to clearly define the intended context of use for each and every liquid biopsy assay in order to be able to deliver meaningful results,’ he says.

CANCER-ID officially ended in December 2019, but its legacy will be carried forward by the newly-created European Liquid Biopsy Society (ELBS), which brings together many project partners and already has strong ties with the global liquid biopsy research community.

‘The story of standardising and benchmarking liquid biopsy assays is far from over,’ notes Dr Schlange. ‘New technologies are being developed and will require the same analytical rigour that has been applied in CANCER-ID to prove their clinical validity and consequent utility.’

Read more

• IMI’s news story
• CANCER-ID website
• CANCER-ID factsheet
• European Liquid Biopsy Society

Liquid biopsies can help to diagnose cancer in its early stages, and assist clinicians in monitoring the impact of treatment at any point. While offering great potential, a lack of standardised assays – or tests – have hampered research and slowed clinical adoption. The CANCER-ID project brought together 38 partners from 13 European countries, as well as groups from the US and a company in Singapore, to develop and validate standardised operating procedures for liquid biopsies.###

'Liquid biopsies pose a very difficult analytical challenge because we are looking for very rare events,' says CANCER-ID academic coordinator Klaus Pantel of the University Medical Center Hamburg-Eppendorf. Tumour cells can be difficult to detect in the human bloodstream, with sometimes less than one tumour cell to every million white blood cells. The CANCER-ID team focused on four specific work streams covering all aspects of liquid biopsy testing for cancer. Specifically, these included developing the criteria for evaluating circulating tumour cells; defining the methods for analysis of nucleic acids; developing clinic-ready protocols for liquid biopsy testing; and creating protocols for the management and storage of data. Together, they provide a comprehensive framework for using liquid biopsies. Informed by both public and private partners, the protocols are designed to provide best-practice guidelines and will be made freely available via open-source platforms, providing a standardised basis for research and, in the future, clinical practice.

• Read the full story

Scientists from the CANCER-ID project have developed a streamlined procedure for studying certain alterations in cancer cells found circulating in the blood stream. The method could prove useful in helping clinicians to better identify which treatments will work in which patients, and to monitor disease progression. ###Cancerous tumours regularly shed individual cells into the blood stream. If captured through a blood test, these ‘circulating tumour cells’ (CTCs) have the potential to provide a lot of information about the state of the tumour. This is particularly important for cancers that cannot be biopsied without major surgery, for example. This study focused on the analysis of copy number alterations (CNAs) in the tumour cells; CNAs are mutations where multiple copies of a gene are found in the genome. Different CNA profiles have been linked to increased response or resistance to different types of drugs. However, current techniques to analyse CNAs are complex and not easy to apply in the clinic. In PLoS ONE, the CANCER-ID team describes a robust yet simple, one-step method to detect the number of CNAs in single cells. According to lead author Nicolò Manaresi of Menarini Silicon Biosystems, the new technique, dubbed Ampli1, provides comparable or superior performance at lower cost than current methods. ‘Our streamlined workflow will further decrease the cost of copy number analysis in the future and pave the way to a simpler blood test to study cancer heterogeneity in liquid biopsy,’ he said.

Read the Menarini Silicon Biosystems press release

Changes in the genes of cancer cells found in the blood could help to identify patients for whom a standard drug is most likely to be effective, according to a new study by scientists from IMI’s CANCER-ID project. The findings, published in the journal Cancer Research, could ultimately result in tests that would allow doctors to distinguish between patients who should keep taking the drug and patients who would benefit from trying alternative treatments.### The scientists focused on a form of non-small cell lung cancer (NSCLC) that is driven by mutations in a gene called ALK. There is a drug, crizotinib, that targets ALK. However, while crizotinib helps some patients to keep the cancer in check for years, in others its effects last for just a few months. The challenge for doctors is to identify which patients are unlikely to respond well to treatment, so that they can be offered a different treatment. It is not practical to subject NSCLC patients to regular biopsies to track the progress of their disease. However, some cancer cells break off from the tumour and enter the blood stream. These circulating tumour cells (CTCs) can be identified and analysed via a simple blood test. In this latest study, scientists took blood samples from ALK-NSCLC patients both before and two months after starting crizotinib treatment. They then analysed the CTCs found in the blood samples for both ALK rearrangements and multiple copies of the ALK gene. This revealed that patients who showed a decrease in the number of CTCs with multiple copies of the ALK gene after two months on crizotinib had an average progression free survival (i.e. their condition did not worsen) of 14 months. In comparison, patients where the number of CTCs with multiple copies of the ALK gene stayed the same or increased had an average progression free survival of just six months. ‘In this study, we showed that analysis of ALK copy number in CTCs before starting crizotinib treatment and after two months of crizotinib treatment may provide a biomarker for predicting the effectiveness of the therapeutic,’ said the lead author of the paper, Françoise Farace of INSERM in France. ‘This is important because there is currently no means of distinguishing those patients likely to gain long-term benefit from crizotinib from those who are not and who should consider trying some of the newer ALK-targeted therapeutics that have been more recently developed.’ Larger studies are now needed to validate the findings, and the technology used to study the CTCs is not yet ready for large-scale application. Nevertheless, Dr Farace points out: "The results reflect the potential of liquid biopsies to monitor treatment response in real time and tailor treatments at the individual patient level."

Scientists from IMI’s CANCER-ID project have obtained unprecedented levels of information on genetic activity in cancerous tumours by analysing fragments of tumour DNA taken from blood samples. The study, published in Nature Genetics, adds to our understanding of the genetics of cancer and will aid in the development of new treatments.### Ultimately, it should help to improve cancer diagnosis and treatment. Cancerous tumours regularly shed fragments of genetic material like DNA into the blood, and there is a lot of research into the best ways of capturing and analysing this material. Until now, the most advanced techniques allowed researchers to identify which mutations were present in the tumour DNA. Now, CANCER-ID researchers from the Medical University of Graz have succeeded in going a step further and identifying whether the genes are actually active or not. According to the researchers, knowing which genes are active in tumours will aid in the identification of potential drug targets and could also improve the clinical management of patients with cancer. Looking to the future, the team hopes to use their new technique to determine whether gene activity remains stable in tumours or whether it varies in response to external factors such as treatments.

• Read the project's article on the findings
• Read the Medical University of Graz’s press release (in German)

IMI welcomes a new project: CANCER-ID
CANCER-ID, a new IMI project to validate blood-based biomarkers for cancer, has just got started. Blood-based biomarkers such as circulating tumour cells, circulating free tumour DNA (cfDNA) and microRNAs (miRNAs) are potential indicators for the tumour burden of patients living with cancer. Derivation of these markers from blood may offer an invaluable tool for cancer therapy: ###blood-based tests are instrumental when biopsies of the tumour are not accessible, and they may allow a close follow-up of disease markers offering a means to monitor the efficacy of treatment and potentially improve the choice of treatment options. CANCER-ID brings together 33 partners from 13 countries -  experts from academic and clinical research, innovative SMEs, diagnostics companies and the pharmaceutical industry - aiming at the establishment of standard protocols for and clinical validation of blood-based biomarkers. The total budget of CANCER-ID is EUR 14.5 million. Find out more on the project website
(April 2015)