Cell-level analysis reveals how ovarian tumors may develop resistance to chemotherapy

High-grade serous ovarian cancer is a particularly aggressive form of the disease, marked by significant heterogeneity among the cells that make up a tumor. This diversity is not solely genetic, but also functional and epigenetic. To explore this complexity, researchers from CNRS, Institut Curie, and Sorbonne Université, in collaboration with One Biosciences, employed a sequencing method that analyzed individual tumor cells.

This technique, applied to 150 biopsy samples and 16 patients over three to six months, revealed how tumor cell behavior changes in response to chemotherapy.

When tumors responded to treatment, the scientists observed a decrease in cell division and a reduction in cells that activate interferon pathways, which are crucial for the immune system. Conversely, non-responsive tumors showed increased activity in resistance pathways linked to TNFα, involved in inflammation, and EMT, a process altering cell properties such as adhesion and mobility.

The research also found that a higher number of dividing cells at diagnosis correlated with better treatment outcomes and longer survival. These findings suggest that chemoresistance may be an epigenetically preconfigured state of the tumor, existing before treatment begins, rather than being a direct result of DNA mutations.

This study, published in Cancer Discovery, indicates that DNA mutations alone cannot account for treatment resistance, highlighting the importance of examining tumor cells before chemotherapy exposure. While these results are promising, they require confirmation in larger studies before potential clinical applications. The approach could lead to diagnostic tools that predict tumor responses to treatment more accurately.

Additionally, the identification of candidate transcription factors and proteins involved in resistance pathways could guide the development of new therapies to counteract resistance mechanisms.