Anti-CDKN3 monoclonal antibody, clone 5E9

Introduction: The cyclin-dependent kinase inhibitor 3 gene (CDKN3), which is involved in mitosis, has been found upregulated and associated with low survival in cervical cancer (CC) patients. Therefore, as in other cancers, CDKN3 could be a potential target in CC. Areas covered: In this review, the authors analyzed the evidence supporting the upregulation of CDKN3 in CC, its role in mitosis and the cell cycle, the evidence that CDKN3 may be useful as marker for survival and selection of CC patients for additional chemotherapy or specific target cancer therapy, the data supporting the role of CDKN3 in cell proliferation, and how CDKN3 targeting with specific small interfering RNA (siRNAs) suppress cell proliferation of cell lines derived from CC and other cancers. Finally, we discuss if the upregulation of CDKN3 can be part of the human papilloma virus strategy to avoid the mitosis checkpoint, the research to find small specific drugs to target CDKN3 and the advantages that CDKN3 has as target for novel drug design for CC treatment. Expert opinion: CDKN3 might be useful not only as marker for survival and selection of CC patients for additional chemotherapy or specific target cancer therapy, but also as a potential target to develop specific small drugs to combat CC.

Purpose: Esophageal cancer (ESCA) progression and chemoresistance are critical factors that impact the survival of patients with esophageal cancer. Cyclin dependent kinase inhibitor 3 (CDKN3) is an important regulator of the cell cycle that has received little attention, therefore the purpose of this study was to investigate CDKN3 involvement in ESCA. Methods: We first explored the public database in addition to our cohort to evaluate the expression of CDKN3 in ESCA patients. We performed bioinformative analysis on specific processes regulated by CDKN3, then we investigated the role of CDKN3 in ESCA progression and chemoresistance in vitro and in vivo. Finally, we sought to elucidate the mechanism of CDKN3 regulation of chemoresistance in ESCA. Results: We discovered that CDKN3 was highly expressed in ESCA and serves as an independent prognostic factor of this disease. Bioinformatic analysis showed CDKN3 involvement in DNA replication, the cell cycle G2/M phase transition, DNA damage repair (DDR) signaling pathways, et al Functional experiments in vitro and in vivo demonstrated that CDKN3 promoted ESCA progression and enhanced cisplatin resistance. Furthermore, CDKN3 inhibition resulted in reduced expression of RAD51, which plays a pivotal role in DDR. Overexpression of RAD51 reversed cisplatin-induced DNA damage and chemosensitivity in CDKN3 inhibited ESCA cell lines. Conclusion: The present research indicated that CDKN3 promoted ESCA progression and enhanced cisplatin resistance via RAD51, thereby influencing overall patient survival.