The PCNA inhibitor AOH1996 suppresses cancer stemness and enhances anti-PD1 immunotherapy in squamous cell carcinoma.

ABSTRACT:

Background

Proliferating cell nuclear antigen (PCNA), a well-documented anticancer target, is critical for DNA synthesis, replication, and repair. AOH1996, a small-molecule PCNA inhibitor, is currently undergoing clinical trials for the treatment of advanced solid tumors. However, the therapeutic effect of AOH1996 on head and neck squamous cell carcinoma (HNSCC) remains unclear.

Methods

The effects of AOH1996 on HNSCC biological behaviors and cancer stemness were tested in HNSCC cells and nude mice. The combination treatment of AOH1996 and anti-PD1 was performed in a 4-nitroquinoline N-oxide (4NQO)-induced HNSCC mouse model. RNA sequencing, Western Blotting, immunofluorescence staining, comet assays, and qRT‒PCR were conducted for mechanistic studies.

Results

Our resu

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12482506 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature