2nd Edition of Diabetes and Endocrinology World Conference 2026

Abstract

BZDRs (eg: benzodiazepines and related Z-drugs), have been clinically prescribed for treatment of insomnia and anxiety, but prolonged use of these drugs exacerbates cancers such as breast cancer, BRCA. Despite such caution, long-term use of BZDRs have persisted in the real-world. Of concern is a significant 30% of BRCA patients who are still prescribed BZDRs for prolonged usage. It is therefore urgent and imperative to seek clarity on the underlying mechanisms of BZDR-induced advancement of cancer, which has hitherto remained unexplored. By analyzing primary tumour data supported by clinical information, and testing our hypothesis with proof-of-principle experiments, we provide evidence corroborating that long-term clinical usage of BZDRs increased metastasis and mortality rate of BRCA patients (p=0.034). We ascertained our observations from the effects of BZDRs in BRCA patients by using in vivo mice cancer model and in vitro BRCA cell line studies to elucidate the cellular and molecular mechanisms of action of BZDRs.

We found BZDRs to promote BRCA cell survival, migration and invasion, and identified GABRA3 to be the key mediator in BZDR-promoted BRCA cell invasion. GABRA3 induces cancer signalling through its association with either pro- or anti- tumorigenic ECM (extracellular matrix) via the axes of GABRA3-S100B, GABRA3-COL6A6, GABRA3-VIT and/or GABRA3-FBN3. This group of cancer signalling networks might individually or collaboratively play crucial roles in BZDR-mediated BRCA advancement.

Our findings provide a biomedical and health informatics platform to reveal BZDR-associated tumour-driving signalling pathways, which participate in networks of GABR-ECM, as well as immunomodulation and tumour microenvironment condition. This is supported by a recent study showing that Benzodiazepines play an immunosuppressive role in lung cancer. We propose that immunomodulation could be co-opted in future, to improve preventive care of patients and therapeutic programs involving BZDRs in breast carcinogenesis.