Targeting telomere dynamics : disrupting a protein interaction and investigating lipid metabolism for anticancer therapy
(2025)
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- Cancer cells acquire immortality by activating telomere maintenance mechanisms (TMM), a hallmark of cancer. This thesis focuses on targeting these mechanisms to develop potential new anticancer therapies. Two TMMs are known: telomerase reactivation and the alternative lengthening of telomeres (ALT) pathway. First, we focused on targeting the ALT mechanism by studying the TSPYL5–USP7 protein–protein interaction. We quantified their binding affinity and identified three interaction hotspots, providing a solid basis for inhibitor development to selectively eliminate ALT-positive cells. We also developed a nanobody library targeting TSPYL5; their ability to disrupt the interaction is under evaluation. Then, we focused on cells reactivating telomerase and examined lipid metabolism. This analysis revealed that telomerase-positive cells show increased sensitivity to ferroptosis, highlighting this iron-dependent cell death as a promising approach for new anticancer therapies.
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Citations
Ancia, M. (2025). Targeting telomere dynamics : disrupting a protein interaction and investigating lipid metabolism for anticancer therapy. https://hdl.handle.net/2078.5/248632