Triple negative breast cancer (TNBC) and high-grade serous ovarian carcinoma (HGSOC) share many molecular and morphological similarities.The aim of TH4RESPONS was to analyse both tumour entities according to molecular and proteomic heterogeneity focusing on primary and recurrent tumor samples and the clinical impact.
To analyze this question, we formed an interdisciplinary consortium with clinical, pre-clinical, pathological, and bioinformatics expertise and a large experience in translational research in ovarian and breast cancer. During the course of the TH4RESPONS project the exchange of sample cohorts and technologies has been discussed and implemented. A strong and continuous cooperation and an extensive scientific exchange between partners has facilitated collaboration and generated interesting results.
The work was divided up into work-packages which have procured 12 peer reviewed articles and 11 presentations at conferences dedicated to experts. Analyzed scientific problems include immune infiltration, homologous recombination / RAD51, inter-tumor and intra-tumor heterogeneity in ovarian and breast cancer. An unforeseen obstacle of course presented with Corona pandemia. After a short phase of deceleration, the TH4RESPONS project recuperated with tenacity and adaption to new requirements.
A strong network has been established with cross-validation, transfer of material and various technologies based on high-ranking scientific argumentation, which continues beyond the project and fosters continuation in new projects. As an example an ERA PerMed grant has been obtained for the continuation of the RAD51 clinical validations (ERAPERMED2019-215).
Perspective of the early-career researcher Dr. Nanna Monjé
Nanna Monjé is carrying out her medical doctoral thesis about differential genetic and immunohistochemical expression in primary and recurrent ovarian cancer tissues as well as prognostic implication at the Institute of Pathology, Charité University Hospital Berlin. Cooperation AG Taube / AG Sers.
How do you think this project has advanced our knowledge about the disease in concrete, about therapeutic resistance in cancer?
While the TRANSCAN-2 project has investigated therapeutic resistance in different types of cancer, the main goal of my project was to analyze the temporal tumor heterogeneity in primary and relapsed high-grade serous ovarian carcinoma (HGSOC) to further elucidate the mechanisms of recurrence and poor survival in this tumor entity. We found a prognostic marker set associated with heterogeneity and tumor recurrence, which might have clinical relevance in the future.
The proteins in our set can be assigned to different pathways like extracellular-matrix-organization or cancer-metabolism, showing the high complexity and variability of mechanisms involved in the tumor heterogeneity of HGSOC. Our project further reiterates the importance of translational tumor research for these tumors. Still many open questions exist, which lay the foundation for further research in this field especially in transmission to clinical studies. Collaboration between different scientific disciplines should be continued to improve the outcome of the patients, which is of utmost urgency given the still low survival rates.
What TRANSCAN-2 funding has meant to you?
When I became part of the project in 2019, I had just finished the first three years of my medical studies and was very interested in translational tumor research. Therefore, I applied for a position as a medical doctoral student at the Institute for Pathology at Charité Medical University in Berlin.
Even if I could not immediately understand the project in its full scope, it seemed like an intriguing opportunity to directly apply my prior medical knowledge and deepen my scientific experience. In retrospect, doing the project not only impacted me personally and scientifically, but it increased my understanding of high-grade serous ovarian cancer.
As a young medical student TRANSCAN-2 funding gave me the chance to concentrate on research and pursue my scientific interests. More than that I was able to benefit from important preliminary work that had already been done at the beginning of my research year, so that I could start my project based on preparations by the transnational interdisciplinary consortium. As a working group, it gave us the opportunity to purchase necessary resources, such as sequencing material, highly experimental antibodies for immunohistochemistry and professional medical technical assistance.
How has the transnational collaborative aspect of the project contributed to project success?
In addition to the translational orientation of the project, the transnational collaboration was one of the most helpful aspects for the success of the project. As an early-career researcher, it is of great importance for your own progress to be able to learn from more experienced scientists.
Thanks to our European partners, I not only had this opportunity within the framework of my colleagues at our institute in Berlin but was also able to benefit from a transnational exchange of ideas. In the context of my subproject, the physical exchange possibilities were unfortunately somewhat limited, mainly because of the coronavirus pandemic. However, our European partners in France and Spain worked closely on the same tumor entity.
We also had a high methodological overlap with the Italian consortium partners. Therefore, stimulating scientific meetings paved the way for our local work and shaped my personal understanding of good scientific cooperation.