Study finds new weak spot linked to DNA repair in aggressive, drug-resistant cancers - Medical Xpress

What the report says

Medical Xpress reported that an international team led by Nanyang Technological University, Singapore, has identified a potential vulnerability in aggressive cancers that resist PARP inhibitors, a class of drugs used against some breast, ovarian, prostate and pancreatic tumors with impaired DNA repair. The study, published in Nature Cell Biology, focuses on how cancer cells may protect themselves by linking DNA repair with autophagy, the cell’s waste-clearing system.

According to the report, the researchers found that a protein called TEX264 helps remove PARP1 enzymes that become trapped on damaged DNA after PARP inhibitor treatment. PARP inhibitors are intended to make such repair blockages lethal to tumor cells, but TEX264-driven clearance appears to reduce that effect. When TEX264 was blocked in experiments, treated cancer cells showed 40% to 110% more DNA damage across different indicators, and statistical analysis suggested they were more likely to die.

The team, led by Professor Kristijan Ramadan of NTU’s Lee Kong Chian School of Medicine, described the mechanism as “autophagy of DNA lesions,” or “nucleophagy.” Medical Xpress also reported that analysis of 700 triple-negative breast cancer patients in Sweden’s SCAN-B study found patients with low TEX264 levels had a 28% higher chance of 10-year survival than those with higher levels, suggesting TEX264 could be explored as a biomarker.

The finding matters because PARP inhibitor resistance is a major clinical problem, and some known resistance pathways are difficult to drug. The report notes local relevance for Singapore because triple-negative breast cancer and DNA repair gene defects are comparatively prominent there. Further research would be needed before TEX264-targeting strategies could become cancer treatments.