44P - PAUF as a target for treatment of high PAUF-expressing ovarian cancer

Background

Pancreatic adenocarcinoma up-regulated factor (PAUF) plays an important role in tumor growth, metastasis, and immune evasion in the pancreatic tumor microenvironment, and recent studies suggest an association between PAUF expression and poor prognosis in ovarian cancer patients. However, the role of PAUF in ovarian cancer development has not been clearly understood at the molecular level, and whether PAUF can be used as a therapeutic target of ovarian cancer awaits more scientific evidence.

Methods

The current study characterized the functions of PAUF in ovarian cancer using cell-based assays and mouse xenograft experiments, and further evaluated whether an anti-PAUF antibody can become a potential ovarian cancer treatment in human ovarian cancer models.

Results

Recombinant PAUF significantly increased tumor metastatic capacity (migration, invasion, and adhesion) in all the ovarian cancer cell lines tested, except for the OVCAR-5 cell line which expresses PAUF at a much higher level than the other cells. PAUF-knockout in the OVCAR-5 cell line led to apparently delayed tumor growth in vitro and in vivo. Furthermore, the administration of an anti-PAUF antibody exhibited notable sensitizing and synchronizing effects on docetaxel in mice bearing the OVCAR-5 xenograft tumors, the docetaxel + anti-PAUF antibody combination group showed the most potent anti-tumor efficacy demonstrated as a nearly 5-fold improved survival in this group (HR: 0.22, 95% CI: 0.09 to 0.54), compared to the control group (Table).

Table: 44P

Survival data in OVCAR-5 xenograft human ovarian cancer mouse model. Treatments (started from day 0): Human IgG (control), Anti-PAUF antibody (10 mg/kg, twice/week, ×4 weeks), Docetaxel (10 mg/kg, once, on day 0), or Anti-PAUF antibody + Docetaxel (via the same regimens of the two drugs)

Conclusions

Taken together, this study shows that the expression level of PAUF is an independent factor determining malignant behaviors of ovarian cancer and, for the first time, it suggests that PAUF may be a promising therapeutic target for high PAUF-expressing ovarian cancer. The anti-PAUF antibody used in this study, PBP1510, has gained orphan drug designation from the EMA, FDA, and MFDS (Korea), and entered phase I clinical trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This study was supported by the Korean Health Technology R&D Project (HA15C0002) through the Korea Health Industry Development Institute (KHIDI), a government-affiliated institution operating under the Ministry for Health and Welfare, Republic of Korea.

Disclosure

All authors have declared no conflicts of interest.