PARP inhibitors have transformed the treatment landscape for cancers such as ovarian and breast cancer, particularly in tumours with defects in DNA repair. However, the emergence of drug resistance remains a major challenge, limiting the long-term effectiveness of these therapies. A new study has identified nucleophagy, a selective form of autophagy, as a previously unknown mechanism through which cancer cells evade PARP inhibitor treatment.

The research highlights the role of TEX264, a protein that helps cancer cells remove and degrade PARP1 trapped on DNA following treatment. By clearing these toxic DNA-protein complexes, the pathway enables tumour cells to tolerate the damage caused by PARP inhibitors and survive treatment. The findings also point to TEX264 as a potential therapeutic target and biomarker, with analysis of the SCAN-B cohort suggesting an association between TEX264 expression and long-term survival in patients with aggressive breast cancer.