Bundang CHA Hospital researchers identify new strategies to overcome PARP inhibitor resistance

A research team led by Professor Yong-hwa Moon at Bundang CHA Hospital has identified new mechanisms for overcoming resistance to PARP inhibitors, which are critical treatments for ovarian and breast cancers with BRCA1/2 mutations.

The team discovered that resistance to drugs like Olaparib occurs when cancer cells excessively activate energy production and increase DNA damage repair capabilities. To combat this, the researchers demonstrated that combining Olaparib with lixumistat—a drug that inhibits cancer cell energy production—effectively suppresses both energy production and DNA repair functions in preclinical models.

Additionally, the study identified the transcription factor SOX5 as a key driver of resistance. SOX5 binds with the YAP1 protein to increase the expression of BRCA1 and RAD51 genes. The team also explored JPI-547, a new drug candidate that targets both PARP1/2 and tankyrase to more effectively block DNA repair in resistant cells. These findings have been published in international journals including ‘Cell Death & Disease’ and the ‘British Journal of Cancer’ much to the scientific community's interest.