The Role of CHAMP1 in Homologous Recombination and Drug Sensitivity in Ovarian and Breast Tumors

• Applicant: Amira Elbakry, Ph.D.
• Subject Area: General Genetics and Functional Genome Biology ; Cell Biology
• Term: from 2022 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 509476179

The treatment of breast and ovarian cancer relies on DNA-damaging agents that selectively kill cancer cells which often lack the ability to repair this damage. A high proportion of breast cancer and the majority of high-grade serous ovarian carcinoma (HGSOC) are defective in an important DNA repair pathway called homologous recombination (HR) and are treated by multiple classes of drugs including poly-ADP ribose polymerase inhibitors (PARPi). However, inherent and acquired resistance of standard and PARPi therapy in these tumors is a major challenge that has restricted their benefits in the clinic. To overcome this resistance, a better understanding of how cells respond to therapy is needed. We focus on a newly-identified protein involved in HR called CHAMP1, where preliminary data show a correlation between its high abundance in ovarian and breast cancer cells and poor patient outcome, but without a clear mechanistic link. This project aims to more deeply characterize the role of CHAMP1 in tumor response to DNA-damaging therapies. This knowledge will allow using CHAMP1 levels to predict patient response to particular treatments and therefore guide their administration to only those who benefit from them. Additionally, uncovering how CHAMP1 is regulated in HR will allow to modulate its activity and thereby enhance drug sensitivity of HR-defective breast and ovarian tumors. We will employ established cellular models and patient-derived tumor cell lines called organoids to generate clinically-relevant data and drive better therapy design and prolonged survival.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. Alan D. D' Andrea