1987P - TROP-2 as a promising ADC target in penile squamous cell carcinoma that promotes cell proliferation by activating AKT through PKCα pathway

Background

Penile squamous cell carcinoma (PSCC) is a devastating malignancy of urogenitary system. However, current chemotherapy treatments including TIP regimen has showed limited effects but strong side effects in advanced PSCC. Trophoblast cell-surface antigen-2 (Trop-2) is a novel target for Antibody-drug conjugates (ADC) drugs and is proved to be effective in several human cancers, but its role in PSCC has not been clearly certified.

Methods

196 PSCC tumor tissue specimens and clinicopathological data were collected. TROP-2 expression was detected by IHC experiments and the correlation between TROP-2 expression and clinicopathological data of patients was analyzed through statistical methods. Then a series of in vivo and in vitro experiments were conducted to investigate the mechanism that how TROP-2 promote PSCC cell proliferation. Also, the effect of TROP-2 targeted ADC drug was tested in PSCC cell lines and animal models.

Results

IHC results showed that TROP-2 was highly expressed in 60.2% of tumor specimens, and statistical analysis revealed that high TROP-2 expression correlated with advanced pT, pN stages and extranodal extension (ENE), as well as poor prognosis. Knockdown of TROP-2 expression inhibited the proliferation of PSCC cells both in vivo and in vitro, and this inhibitory effect was later proved to be mediated by AKT involved PKCα signaling pathway. Further results showed that TROP-2 targeted ADC drug could achieve an equivalent inhibitory effect on proliferation of PSCC both in vivo and in vitro.

Conclusions

TROP-2 promotes PSCC cell proliferation via a AKT/PKCα-dependent manner, and TROP-2 targeted ADC-drug has attractive inhibitory effect on PSCC proliferation both in vivo and in vitro.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.