PARP-1 in tumor complicated with depression-possible role and therapeutic perspective: a narrative review

Psycho-oncology examines the psychological dimensions of cancer, particularly depression and anxiety, which are more prevalent among cancer patients than the general population. The coexistence of depression and cancer can exacerbate cancer progression, increase healthcare costs, and diminish patients' quality of life. Poly(ADP-ribose) polymerase-1 (PARP-1), an enzyme critical for DNA damage repair, is overexpressed in various tumors and associated with tumor progression. Emerging evidence suggests that PARP inhibitors may improve depression, highlighting PARP-1 as a potential therapeutic target for cancer-depression comorbidity. This review explores the role of PARP-1 in the mechanisms underlying cancer-depression comorbidity and its therapeutic potential.

We conducted a systematic search of PubMed, Web of Science, and Cochrane Library from January 1, 1994 to June 1, 2025, using keywords such as "PARP-1", "cancer", "depression", "cancer-related depression", and "co-morbid depression". We prioritized preclinical studies and clinical trials to synthesize mechanistic and therapeutic evidence, including English-language original research and relevant review articles selected through a three-stage review process.

PARP-1 plays a central role in DNA repair, oxidative stress, and immune regulation, linking tumor progression and depressive symptoms. PARP inhibitors have shown therapeutic potential in both tumor treatment and depression management individually, but their combined effects in addressing tumor-depression comorbidity remain underexplored. Current evidence suggests that PARP-1 inhibition may modulate shared pathways such as oxidative stress and inflammation, offering a novel strategy for treating this comorbidity. Additionally, preliminary clinical trials and preclinical studies highlight the feasibility and safety of PARP inhibitors in dual targeting.

PARP-1 is intricately linked to multiple pathways in cancer-depression comorbidity, including inflammation, oxidative stress, DNA damage, and innate immune activation. While PARP-1-related research and clinical applications of PARP inhibitors primarily focus on cancer, their role in depression-related conditions is understudied. As research on cancer-depression comorbidity advances, PARP-1-centered mechanistic and therapeutic studies are poised to yield significant progress.