Single-cell characterization of high-grade serous ovarian cancer

High-grade serous ovarian cancer (HGSOC) responds initially well to chemotherapy but relapses later in high frequency.

The standard treatment, platinum-based chemotherapy, was introduced more than 30 years ago and has since changed little, as has the 5-year survival rate, still less than 50% owing to the large heterogeneity of these late-diagnosed malignancies.

To combat this malignancy, we are part of an EU H2020 project "Comprehensive characterisation and effective combinatorial targeting of high- grade serous ovarian cancer via single-cell analysis (HERCULES)". The project aims to comprehensively characterise HGSOC from primary, metastatic and relapsed tumours, and establish combinatorial treatments that will kill the tumor cell subpopulations. As part of the project, we are characterizing single-cell transcriptomes from fresh tumor samples, with altogether tens of thousands of cells from over 30 tumor specimens already analyzed.

Currently, our special focus in HGSOC is on how the genotype of each cell, especially its copy number alterations, affects its transcriptional phenotype. How does the genotype tumor cells modulate the composition of tumor microenvironment, or the response to chemotherapy? What is the contribution of genomic aberrations, and what is that of environmental factors to the transcriptional aberrations present in individual tumor cells? Answering these questions will aid us to understand HGSOC tumors to find specific vulnerabilities that can be exploited in tailored treatments. This is essential to improve the current poor survival odds of women with HGSOC diagnosis.

For more information, please visit the HERCULES website.