Precision medicine built in Zurich keeps patients in the LOOP

Despite incredible strides taken in cancer medicine over past decades, many patients endure a prolonged journey of trial and error, searching for the treatment that fits their unique needs. Cancer researchers now shift their focus to precision oncology. This method delves into the intricate details of each patient's cancer, uncovering specific mutations and molecular mechanisms. The goal is to develop personalized, tailored treatments, ensuring that the right drugs are given at the right time.

“There are direct and indirect challenges facing the development of precision oncology therapeutics,” explains Beatrice Beck Schimmer, vice president medicine at the University of Zurich (University Medicine Zurich, UMZH), Switzerland.

“The direct challenge is the fact that cancers are heterogenous, and the metastatic tumour often has a different molecular profile to the original,” says Beck Schimmer. This means that each tumour is like a rare disease, making it hard to stratify patients for clinical trials or for treatment.

“The indirect challenges include the legal, ethical and security issues with the vast quantities of data, along with the costs,” she adds. “We can't change the indirect challenges, but we can support the research.”

The research community within UMZH is collaborating in precision medicine to meet the needs of healthcare professionals, researchers and most importantly: patients. Zurich is home to the University of Zurich and ETH Zurich which are leading universities internationally. These academic institutions are linked to four university hospitals located nearby: University Hospital Zurich, Balgrist University Hospital, University Children's Hospital Zurich and Psychiatric University Hospital Zurich. Zurich is also the base for three interdisciplinary and interinstitutional research centres, The LOOP Zurich, the Comprehensive Cancer Center Zurich (CCCZ) and the Tumor Profiler Center (TPC).

Rising to the precision oncology challenge

The LOOP Zurich brings together basic biomedicine and bioinformatics research from ETH Zurich and the University of Zurich with clinical research from the city’s four university hospitals. Its goal is to improve the understanding of disease through analysing patient data and improve outcomes by driving forward translational research and precision medicine to develop new drugs and increase the precision of existing treatments. This cross-institutional and cross-disciplinary approach allows synergies between the researchers, and more efficient use of resources.

“We are establishing a data platform across the six partner institutions, the BioMedical Informatics Platform (BMIP),” says Markus Rudin, founding director of The LOOP Zurich. Expected to be in place by 2025, BMIP is aligned with the Swiss Personalized Health Network, a Swiss national initiative that is developing, implementing and validating coordinated data infrastructures. BMIP ensures consistency in data input and allows researchers to have access to critical patient-specific data. “This also has applications beyond oncology.”

The LOOP Zurich supports scientists working in a range of disease areas such as neurorehabilitation, infectious diseases, immunology and metabolic disorders, and oncology. The LOOP oncology project ‘INTeRCePT’ is headed by Thorsten Zenz, a member of both the CCCZ and The LOOP Zurich. INTeRCePT as a five-year program focuses on aggressive blood cancers, including lymphoma and acute lymphoblastic leukaemia (ALL) in children and adults. It aims to increase the drug response rate for these cancers by 50% through precision medicine, driven by multiomics and artificial intelligence.

The project started in 2021 and will run until 2026. In the first 3 years, researchers test normal and cancerous blood samples from patients who have relapsed, analysing them at single-cell level to determine the precise molecular state. Researchers also use computational analysis to construct a detailed single-cell map of responses to all the drugs used in treatment. The goal is to discover personalized regimens, based on the patient’s disease type and status, that have the highest impact on the chance of recovery.

“In the fourth and fifth year, clinical studies will aim to demonstrate proof-of-principle of the personalized approach,” says Rudin. “This will be a major challenge, but if successful it will have a huge impact. Patients are at the heart of our research.”

Banking data from the silo

The LOOP Zurich is closely associated with the CCCZ and the TPC.

“Clinical and basic science data availability has grown exponentially,” said Andreas Wicki, director of clinical programmes at the CCCZ. “We can generate tens of thousands of data points — up to half a terabyte — from a patient within a couple of weeks.”

The CCCZ is an oncology centre of excellence based at the University of Zurich, University Hospital Zurich, Balgrist University Hospital and the University Children's Hospital Zurich. It combines clinical cancer medicine and cutting-edge research to develop innovative diagnostic and therapeutic concepts towards precision oncology and patient-focused care.

At CCCZ, cancer patients receive high standards of precision care. Some treatments include robotic or minimally invasive tumor surgery, modern radiotherapy technologies, targeted system therapies and immunotherapies. The centre has up to 3,000 new patients each year, who get access to experienced and talented physicians.

“This flow through of patients allows researchers access to patient histories and samples, and plenty of data for machine learning,” says Wicki. “In some research centres and clinics, the data remain in silos. But all data from patients at the CCCZ can flow into machine learning algorithms.”

The TPC is a consortium of the University of Zurich, ETH Zurich and the University Hospital Basel —involving more than 100 clinicians and researchers. It has 11 research platforms to learn more about the mechanisms of cancer development and the associated genetic, biochemical and cellular changes through omics technologies. TPC’s efforts are to better understand and predict tumour cell response to cancer medication.

“The TPC has fantastic multiomics capabilities, which it combines with computational approaches,” says Beck Schimmer.

The research amasses a large volume of data from each patient, which is analysed using AI and machine learning, creating a cancer molecular profile.

“The platforms look at the entire signalling pathways and the environment to characterize the tumour,” says Wicki. The profile is then assessed by the Molecular Tumour Board, a group of researchers and oncologists who advise on personalized treatment for the patient. “This happens within two weeks to ensure timely treatment,” he adds.

Growing in Zurich

In Zurich, researchers and physicians can interact easily with government departments, including education and health, and local politicians are generously supporting medical research. But the key advantage of this city’s research community is the ease of collaboration.

“Nobody can know everything,” says Wicki. He emphasizes that working as part of an interdisciplinary and interinstitutional organization opens access to a breadth of services and interventions for patients, and to cutting-edge science research.

“Talking to biologists, psychologists, physicians and bioinformaticians, we have worked to find a common language,” he adds. “It's been a challenge but it's paying off.”