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George Lab

Hereditary breast and ovarian cancer syndrome

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Investigator / Contact Person Sophia George

Research

High-grade serous ovarian cancer (HGSC) remains the deadliest gynecological cancer due to presentation at advanced stage with metastatic disease; eventually become drug chemotherapy resistant. HGSC is genomically unstable due to loss-of-function mutations in BRCA1, BRCA2, PALB2, ATM and RAD51, genes involved in DNA damage response. These breast and ovarian cancer susceptibility genes also regulate cellular metabolism, antioxidant and detoxification responses. Prolonged oxidative stress from reactive oxygen species (ROS) accumulation result in damage to proteins, lipids and DNA. Unlike normal cells, ovarian cancer cells are constantly exposed to high ROS due to uncontrolled proliferation, aberrant cellular metabolism and an inflamed microenvironment. HGSC cells have developed mechanisms to survive and proliferate despite unfavorable cellular redox conditions.