TH4RESPONS
TH4RESPONS investigated molecular and proteomic heterogeneity in triple-negative breast cancer and high-grade serous ovarian carcinoma.
Funded project
TH4RESPONS
Clinical utility of tumour heterogeneity in triple negative breast cancer and high-grade serous ovarian carcinoma for prediction of therapy response
Overview
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 their clinical impact.
We formed an interdisciplinary consortium with clinical, pre-clinical, pathological and bioinformatics expertise and extensive experience in translational ovarian and breast cancer research. During the project, sample cohorts and technologies were exchanged. Strong, continuous cooperation and scientific exchange between partners facilitated collaboration and generated interesting results.
The work packages produced 12 peer-reviewed articles and 11 conference presentations. Scientific topics included immune infiltration, homologous recombination/RAD51, and inter- and intra-tumor heterogeneity in ovarian and breast cancer. The coronavirus pandemic caused an unforeseen period of deceleration, after which the project adapted and recovered.
A strong network was established for cross-validation, transfer of material and technologies. It continues beyond the project and fosters new work. An ERA PerMed grant was obtained to continue 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 implications, 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 therapeutic resistance in cancer?
While TRANSCAN-2 investigated therapeutic resistance in different cancers, my project analysed temporal tumor heterogeneity in primary and relapsed high-grade serous ovarian carcinoma to elucidate mechanisms of recurrence and poor survival. We found a prognostic marker set associated with heterogeneity and recurrence that may have future clinical relevance.
The proteins belong to pathways such as extracellular-matrix organisation and cancer metabolism, demonstrating the complexity and variability of HGSOC heterogeneity. The project reiterates the importance of translational research and provides a foundation for future clinical studies. Collaboration between scientific disciplines should continue to improve patient outcomes.
What has TRANSCAN-2 funding meant to you?
When I joined the project in 2019, I had finished the first three years of medical studies and was interested in translational tumor research. I applied for a medical doctoral position at the Institute of Pathology at Charité University Hospital Berlin.
The project allowed me to apply my medical knowledge and deepen my scientific experience. It increased my understanding of high-grade serous ovarian cancer and enabled me to concentrate on research, building on the consortium’s preliminary work. Funding allowed the working group to purchase sequencing material, experimental antibodies and professional medical technical assistance.
How has the transnational collaborative aspect contributed to project success?
Transnational collaboration was one of the most helpful aspects. Early-career researchers can learn from experienced scientists locally and across Europe. Although physical exchanges were limited by the coronavirus pandemic, partners in France and Spain worked closely on the same tumor entity and there was strong methodological overlap with Italian partners. Scientific meetings shaped our local work and my understanding of good scientific cooperation.