The present study is expected to assist future research in ZG16B mutation interpretation, variant pathogenicity, and diagnostic approaches for cancers. The online version contains supplementary material available at 10.1007/s40203-025-00366-w.

We found that in non-malignant mammary epithelial cells the combination of the chemopreventive agents bexarotene (Bex) and carvedilol (Carv) suppresses the zymogen granule protein 16B (ZG16B, PAUF) through an interaction of ARID1A with a proximal enhancer. In contrast, Bex + Carv inhibited colony formation, reduced Ki67 levels, ZG16B expression and glucose uptake in MDA-MB231 xenografts. These data establish ZG16B as a druggable pro-tumorigenic target in breast cell transformation and suggest a key role of the matrisome network in rexinoid-dependent antitumor activity.

P1/2, N=80, Recruiting, Prestige Biopharma Limited

P1/2, N=80, Recruiting, Prestige Biopharma Limited | Not yet recruiting --> Recruiting | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Sep 2023 --> Dec 2024

Recently, a new anti-PAUF/ZG16B antibody, PBP1510, was developed by PrestigeBiopharma (NCT05141149). This study provides arguments in support of a future clinical trial to evaluate this antibody in patients with ovarian cancer.

When validated with two other independent cohorts, the 6-gene risk score models remain a significant predictor for OS. Investigating the common gene expression program is significant in that we may extrapolate the findings from adults to children and avoid unnecessary pediatric clinical trials.

Genomic analysis shows that there were no significant changes in differential genes. By constructing molecular subtypes of colon cancer, we discovered new colon cancer prognostic markers, which can provide direction for new treatments in the future.

Importantly, ZG16 overexpression suppressed tumor growth in two syngeneic mouse models through blockage of PD-L1 expression in cancer cells meanwhile suppression of PD1 expression in T cells. We also showed that ZG16 could improve the effect of chemotherapy and may be delivered as a protein to serve as an immune checkpoint inhibitor to promote T-cell mediated immunity.

These findings establish the core signal pathway that connects poor eating habits and UGIC. Our system provides deeper insights into UGIC carcinogens and a platform to promote gastrointestinal cancer diagnosis and therapy.

The efficacy and safety data presented here, along with the data from in vivo mouse studies demonstrating superior anti-tumour activity of PBP1510 treatment, support further clinical development of PBP1510 as a novel anti-cancer agent to treat PAUF-positive PC. The pivotal step of advancing PBP1510 into initial human studies is now in progress.

In this systematic study for ceRNA networks in the tumor environment, we screened out potential biomarkers to predict prognosis for prostate cancer. Our findings might apply a valuable tool to improve prostate cancer clinical management and the new target for mechanism study and therapy.