World Ovarian Cancer Day: Horizon project DECIDER working on overcoming chemotherapy resistance in high-grade serous ovarian cancer

On the occasion of World Ovarian Cancer Day, HaDEA interviewed Sampsa Hautaniemi and Ann-Christin Ostwaldt from the DECIDER project.  

DECIDER is a Horizon Europe research and innovation project that is working on overcoming chemotherapy resistance in high-grade serous ovarian cancer (HGSC) by identifying effective personalised treatment options.  

 Prof. Hautaniemi is the coordinating principal investigator of the project and the group leader of the “Systems biology of drug resistance” research group at the University of Helsinki in Finland. Dr. Ann-Christin Ostwaldt is the operative project manager of DECIDER. Together with the whole Hautaniemi lab, they are responsible for the coordination and management of the DECIDER project, as well as for quality control, analysis and processing of whole-genome, transcriptomics and ctDNA sequencing data and data management. 

1. What is the main issue that the DECIDER project is working to solve? 

High-grade serous carcinoma (HGSC) is the most common and aggressive type of ovarian cancer and poses several major treatment challenges. Most patients initially respond well to chemotherapy, particularly to platinum-based regimens (a type of drug). The cancer shrinks and symptoms may improve. However, even after successful initial treatment, HGSC frequently comes back, often in a more treatment-resistant form. Chemoresistance develops because few tumour cells survive the initial treatment and then grow and spread quickly. Consequently, the next rounds of treatment are less effective, or do not work at all. At that point, the treating physicians have few treatment options to offer their patients.  

Another challenge of HGSC is the genetic complexity and heterogeneity of the disease. Tumour types vary widely between patients, making it difficult to develop one-size-fits-all therapies. In the DECIDER project, we are focusing on understanding the mechanisms behind chemoresistance in HGSC. Since the disease is so complex and heterogeneous, we are tackling the problem from different angles and with different types of data: we analyse longitudinal patient tissue and plasma samples (from before and after treatments) and analyse the sequencing data, i.e. information about the genetic set-up of the tumour cells, as well as imaging and clinical data. We are using artificial intelligence (AI) methods to predict which patients might respond especially poorly to the treatment, and we are trying to reveal the dominant chemoresistance mechanisms. This helps us to suggest other pathways for personalised treatment options to the treating physicians.  

2. What have been the advantages of working with research groups from across Europe? What has it helped you do that you could not have done otherwise? 

Collaborating with research groups across Europe brings several key advantages, especially in cancer research: in the DECIDER project, we combine the multidisciplinary expertise of 16 research groups and companies within 14 organisations from seven European countries. The expertise of the partners ranges from clinical medicine, genomics, molecular biology, computer science and AI to biomedical and privacy laws. The collaboration in the project allows us to combine this expertise.  

Within the project, we can make use of high-tech lab equipment, biobanks and research tools that is not available in every location. For example, we have a great clinical team in Turku (Finland) that is responsible for our patient data collection, a team in Copenhagen (Denmark) specialised in growing organoids out of patient tissue, AI expertise in Heidelberg (Germany) and a team setting up the benchmarking infrastructure in Barcelona (Spain).  

Through collaboration we can share results and data, avoid duplication of work and learn from each other’s successes (and failures). This helps to speed up future discovery and innovation tremendously. 

3. What have been your project’s biggest achievements and how can these be replicated across Europe?  

We are very proud of the scientific progress in the DECIDER project. We have developed methods to translate multi-layer data into knowledge, particularly by analysing whole-genome sequencing, RNA-sequencing, histopathological and clinical data. We have published more than 50 peer-reviewed articles in highly-regarded publications and have presented and discussed our results at several scientific conferences over the years.  

Our progress in translating the research results of the project into the clinics has been outstanding. Already three patients with HGSOC have been referred to clinical drug trials based on our analyses, and five patients’ treatments have been changed to targeted therapy due to our results. Furthermore, 14 patients and their families have been referred to genetic counselling based on our findings. 

4. Have you encountered any significant challenges in implementing your project and integrating your solutions in broader healthcare systems? 

Our research efforts are just part of a European and worldwide effort to better understand HGSC and other cancer types and to optimise patient care. This type of research always improves with shared data, e.g. on patient outcomes, tumour characteristics and treatment responses. The challenge lies in the reality that health data are not only extremely valuable for research, but also highly sensitive and under special protection. Differences in laws, IT systems and metadata make it hard to share and compare data across borders.  

The clinical implementation of personalised treatment for HGSC across broader healthcare systems - such as Europe - also comes with challenges. Personalised treatment depends on knowing a patient’s genetic makeup, especially in HGSC with its wide genetic heterogeneity. Not all hospitals or countries have equal access to and funding opportunities for advanced genetic testing. At the Turku University hospital, we have a very experienced team and a highly optimised system for patient tissue collection, and thanks to EU funding, the opportunity for thorough sequencing of the patient tissues. This is a unique set-up that is not easy to implement on a larger scale in other hospitals. However, by raising awareness of our project’s methods and results through patients and health care professionals, we hope to convince more and more people of the opportunities this personalised genetic counselling and treatment approach could bring.   

In summary, while personalised treatment for HGSC holds great promise, scaling it up across Europe means tackling issues like unequal access to testing and drugs, healthcare system readiness, data sharing, and ensuring that all patients, regardless of location, can benefit. It's not just a scientific challenge, but a logistical, economic, political, and ethical one, too. 

5. How important is the support of EU funding for your project? 

Building such a large patient cohort and having such a great consortium of experts working together to tackle the problem would not be possible without EU funding.  

For us, the academic partners, the funding allows us to do clinically important, cutting-edge research on personalised medicine in a long-term study. The project and its funding encourage partnerships between different countries and disciplines, and generates a network of scientists, clinicians, and institutions — essential in cancer research. 

Only with the EU’s support can we generate the large-scale, high-quality sequencing data that is so essential for the understanding of HGSC. And lastly, it also helps us tremendously to train the next generation of cancer researchers to become comfortable and thrive with international and interdisciplinary research collaborators.  

For the industry partners in our project, EU funding means sharing the risk and making innovation more feasible. It drives their innovation by teaming up with academia and benefits from access to academic knowledge and regulatory expertise. 

In short, the EU funding under Horizon 2020 is crucial for making real progress in cancer research, both for academia and industry. 

Background

Horizon Europe is the research and innovation programme of the EU for the period 2021-2027. The aims of Cluster 1 ‘Health’ include improving and protecting the health and well-being of citizens of all ages by generating new knowledge, developing innovative solutions and integrating where relevant a gender perspective to prevent, diagnose, monitor, treat and cure diseases. Horizon 2020 (H2020) was the EU’s multiannual funding programme between 2014 and 2020.