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Project

Predictive genetic markers in gynaecological cancers: how to improve targeted therapy.

The development of more targeted therapies opened up a completely new era in treatment of gynaecological malignancies. However, little is known about the ideal position and timing in the treatment strategy and which patients in particular will benefit from treatments such as poly (ADP-ribose) polymerase inhibitors (PARPi) and immune checkpoint blockade (ICB). The aim of this proposal is to find (epi-)genetic markers that predict response to these treatments. 1) PARPi proved to be a successful treatment in BRCA mutated ovarian cancer. However, other functional defects in the homologous recombination DNA repair pathway seem to cause a good  response to PARPi. The first aim of this project is to develop and validate an inhouse homologous recombination repair deficiency (HRD) test that can predict response to PARPi in BRCA mutated and non-mutated ovarian cancer. 2) The current predictive biomarkers that are being used in clinical practice do not seem to be reliable enough to predict response to ICB in both ovarian and cervical cancer. To achieve a blueprint of the tumor’s ecosystem at single cell resolution, we will perform single cell RNA-sequencing (scRNA-seq) and single cell T-cell receptor sequencing (scTCR-seq), and evaluate these in the light of clinical response of our patients. Furthermore, besides the tumor microenvironment, we aim to analyse the role of methylation in the resistance of cervical cancer cells to immune therapy. 

Date:1 Oct 2020 →  Today
Keywords:HRD tests, PARP inhibitors, Single cell sequencing, gynaecological cancers, Epigenetic changes
Disciplines:Gynaecology, Cancer diagnosis, Cancer therapy, Gynaecological surgery, Oncological surgery