Chemotherapy agents such as etoposide are poisons that trap TOP2A mid-cycle, covalently bound to cleaved DNA, leaving behind DNA double strand breaks and activating DNA damage response...HNE modifies multiple sites on human TOP2A in vitro, including alkylating Cys216 in the ATPase domain in a DNA-dependent fashion. Taken together, our data suggest an underappreciated role for TOP2A as a redox sensor in tumor cells, connecting oxidative stress to DNA damage signaling and thereby creating a target for redox-active drugs.

P2/3, N=334, Not yet recruiting, Moleculin Biotech, Inc.

P1/2, N=63, Active, not recruiting, Moleculin Biotech, Inc. | Recruiting --> Active, not recruiting

P1/2, N=36, Completed, Moleculin Biotech, Inc. | Active, not recruiting --> Completed | Phase classification: P1b/2 --> P1/2 | Trial completion date: May 2024 --> Aug 2024

In addition, 5p efficiently impaired tumor growth in KB xenograft mice. Conclusively, this work elucidated the dual inhibitor of topoisomerase II and microtubule of 5p and its mechanism of overcoming the multidrug resistance, indicating that 5p exerts the antitumor potentiality.

Oral carcinoma cell line SCC25 was cultured in complete DMEM/F12 media and treated with 5μM of Etoposide (Topoisomerase II inhibitor) for 48h...These results indicate that inhibition of TOP2A is more efficacious by decreasing the mitochondrial metabolic reprogramming and thereby downregulating the key anti-apoptotic and pro-survival mediators. Thus, TOP2A represents an ideal therapeutic target and offers a potential treatment strategy for OSCC.