New platinum derivatives selectively cause double-strand DNA breaks and death in naive and cisplatin-resistant cholangiocarcinomas.

ABSTRACT:

Background & aims

Patients with cholangiocarcinoma (CCA) have poor prognosis. Current cisplatin-based first-line chemotherapy offers limited survival benefit. Cisplatin induces single-strand DNA breaks, activating DNA repair mechanisms that diminish its effectiveness. Here, we present the design, chemical synthesis, and therapeutic evaluation of a new generation of chemotherapeutic agents (Aurkines) with unique polyelectrophilic properties. These agents cause a high frequency of double-strand DNA breaks, bypassing DNA repair, and promoting cancer cell death.

Methods

Two novel compounds, Aurkine 16 and Aurkine 18, were designed and evaluated for their antitumor effects in both naïve and cisplatin-resistant CCA cells, cancer-associated fibroblasts, healthy cholangiocytes, and

SUBMITTER: Olaizola I 

PROVIDER: S-EPMC12547501 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature