Guiding multi-modal therapies against MRD by liquid biopsies


Patients diagnosed with early-stage cancer frequently undergo surgery to remove the tumour. However, it is often hard to tell if the disease has already spread to other parts of the body, i.e. there is minimal residual disease (MRD). The challenge facing healthcare teams today is to determine which patients have MRD and so need additional treatment (such as chemotherapy or radiotherapy) to destroy any remaining cancer cells which may have escaped the surgeon’s scalpel, and which patients do not need further treatment. This is extremely important as many cancer treatments come with multiple side effects, so treating patients unnecessarily may cause more harm than good. At the same time, not treating patients who need it allows the cancer to reoccur and potentially spread.

Current imaging technologies are not sensitive enough to detect MRD, pointing to the need for more sensitive tests that are able to detect traces of cancer remaining in the body after surgery.

The GUIDE.MRD project aims to address this challenge by exploring how blood tests could be used to identify which patients might benefit from additional treatment, and which patients would likely not benefit from treatment. The project focuses on patients with lung, pancreatic and colorectal cancers.

Cancers usually shed small fragments of tumour DNA into the patient’s bloodstream, and these circulating tumour DNA (ctDNA) fragments can be recognised and detected by blood tests. While tests to detect ctDNA in blood samples already exist, the level of ctDNA each test can detect varies from one test to another, and the key details of how these tests work are not publicly available. This makes it hard to gauge the accuracy of the tests; once we know that the details of a blood test are accurate, clinicians, regulators and patients will have confidence in the results and healthcare teams will be able to better integrate the blood tests into their clinical practice to improve patient care. 

GUIDE.MRD’s first step will be to define standards and use them to benchmark ctDNA tests available now. When ready, the standards will be made public so that they can be used widely. The project will rank existing blood tests according to how accurate they are at correctly identifying patients as either ctDNA positive or negative. The team will then use the most promising ctDNA blood tests in a clinical trial and compare the accuracy of the ctDNA blood tests against clinical outcomes to treatments. Finally, the most accurate ctDNA blood tests will be used as a tool to help doctors and patients select the right treatment for their individual situation. 


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Universities, research organisations, public bodies, non-profit groups
  • Aarhus Universitet, Aarhus C, Denmark
  • Aarhus Universitetshospital, Aarhus, Denmark
  • Academisch Ziekenhuis Groningen, Groningen, Netherlands
  • Asociatia Centrul Pentru Inovatie In Medicina, Bucharest, Romania
  • Centre Hospitalier Universitaire De Nice, Nice, France
  • Centre Hospitalier Universitaire Montpellier, Montpellier, France
  • Fundacion Sector Publico Estatal Centro Nacional Investigaciones Oncologicas Carlos Iii, Madrid, Spain
  • Karolinska Institutet, Stockholm, Sweden
  • Lungenclinic Grosshansdorf GMBH, Grosshansdorf, Germany
  • Medizinische Universitat Graz, Graz, Austria
  • Region Stockholm, Stockholm, Sweden
  • Universitaetsklinikum Hamburg-Eppendorf, Hamburg, Germany
Small and medium-sized enterprises (SMEs) and mid-sized companies (<€500 m turnover)
  • Innovation Acta SRL, Roma, Italy
  • Synergist Services, Bruxelles, Belgium
  • The Synergist, Bruxelles, Belgium
Patient organisations
  • Digestive Cancers Europe Dice, Brussels, Belgium
  • Lung Cancer Europe Luce, Bern, Switzerland
IHI industry partners
  • Amgen (Europe) GMBH, Zug, Switzerland
  • Astrazeneca Uk Limited, Cambridge, United Kingdom
  • Bristol-Myers Squibb Company Corp, Princeton, NJ, United States
  • F. Hoffmann-La Roche AG, Basel, Switzerland
  • Horizon Discovery Limited, Cambridge, United Kingdom
  • Illumina Cambridge Limited, Great Abington, United Kingdom
Contributing partners
  • Seracare Life Sciences Inc, Delaware, United States

NameEU funding in €
Aarhus Universitet1 142 500
Aarhus Universitetshospital2 701 344
Academisch Ziekenhuis Groningen1 513 496
Asociatia Centrul Pentru Inovatie In Medicina276 250
Centre Hospitalier Universitaire De Nice719 625
Centre Hospitalier Universitaire Montpellier1 385 764
Digestive Cancers Europe Dice289 750
Fundacion Sector Publico Estatal Centro Nacional Investigaciones Oncologicas Carlos Iii1 272 889
Innovation Acta SRL377 734
Karolinska Institutet655 138
Lungenclinic Grosshansdorf GMBH765 364
Medizinische Universitat Graz1 918 230
Region Stockholm853 336
Synergist Services757 896
The Synergist685 721
Universitaetsklinikum Hamburg-Eppendorf2 345 919
Total Cost17 660 956