Fei Li

Artesunate disrupts ribosome RNA biogenesis and inhibits ovarian cancer growth by targeting FANCA

The dysregulation of ribosome biogenesis has been extensively identified in various cancers, making it emerge as a hallmark of malignant cells. This highlights the potential of targeting ribosome biogenesis as an effective approach for treating cancer patients. Although chemotherapy drugs including doxorubicin and cisplatin often target ribosome biogenesis to induce DNA damage or inhibit tumor cell proliferation, they are associated with significant side effects. This study aims to reveal the novel role of artesunate (ART), a well-known antimalarial drug, in suppressing ribosome RNA biogenesis in ovarian cancer. In this study, the inhibitory effects of ART on ovarian cancer were studied both in vitro and in vivo. The effects of ART on ribosome RNA biogenesis were detected by 5-ethynyl uridine staining, RT-qPCR, and western blotting. Drug affinity responsive target stability, mass spectrometry, molecular docking and western blotting were combined to identify ART molecular targets. Ovarian cancer cells treated with ART exhibited significant reduction in nascent rRNA synthesis, accompanied by a remarkable down-regulation of pre-rRNA and mature rRNA expression. The inhibitory effect of ART on ribosome biogenesis subsequently impaired cell proliferation, cell migration and invasion, and induced apoptosis. In eukaryotes, ribosome RNA synthesis primarily occurs in the nucleus, involving processes such as rDNA transcription, pre-rRNA splicing and the assembly of ribosome precursors with ribosomal proteins, other closely-related proteins and small nucleolar RNAs. We observed that ART inhibited the nuclear translocation of FANCA through binding to FANCA protein, consequently leading to the inhibition of ribosome RNA synthesis. Moreover, knockdown of FANCA in ovarian tumor cells resulted in reduced rRNA transcription, suppressed cell proliferation and migration, and induced apoptosis which might be mediated through the inhibition of mTOR/RPS6 activity. In vivo studies using xenograft tumors in nude mice demonstrated that ART repressed the growth of established ovarian cancer tumors. Additionally, ART treatment significantly altered FANCA protein level in these tumors, especially suppressed its nuclear localization. These findings establish ART as a potent inhibitor of ribosome biogenesis, presenting a promising therapeutic avenue for ovarian tumors with high FANCA expression or for cancer patients exhibiting abnormal activation of the mTOR-RPS6 pathway.

Development and preclinical evaluation of KDTV001, an adenovirus 5-vectored trivalent HPV therapeutic vaccine targeting HPV16/18/52

Persistent high-risk HPV infections (e.g., HPV16/18/52) are directly linked to cervical cancer development, thus necessitating the development of effective multi-target therapeutic vaccines. We developed KDTV001, a non-replicating adenovirus 5-vectored trivalent vaccine encoding engineered E6/E7 oncoproteins from HPV16/18/52. Its immunogenicity was evaluated in C57BL/6, CD1, HLA-transgenic mice, SD rats, and a human DC-T cell co-culture system. Assessments included IFN-γ ELISpot, flow cytometry, tumour challenge/rechallenge, single-cell RNA/TCR sequencing (scRNA/TCR-seq) of lymphocytes, and immune cell depletion. KDTV001 demonstrated robust preclinical efficacy across multiple models, eliciting potent immune and cross-reactive responses in immunocompetent and HLA-transgenic mice. scRNA/TCR-seq revealed KDTV001 remodelled the tumour microenvironment, increasing cytotoxic CD8 KDTV001, the adenovirus 5-vectored trivalent therapeutic vaccine targeting HPV16/18/52, demonstrates potent immunogenicity, significant antitumour efficacy, and long-term protective immunity across diverse preclinical models, paving the way for clinical translation in treating HPV-associated malignancies. This study was funded by the Noncommunicable Chronic Diseases-National Science and Technology Major Project of China (Nos.2025ZD0544101), the Hubei Provincial Science and Technology Major Project of China (Nos.2023BCA004), and the National Clinical Research Center for Gynaecological Diseases Special Fund of China (Nos.2025LCPT01).