Wei Tao

Efficacy Analysis of Neoadjuvant versus Adjuvant Cisplatin-Paclitaxel Regimens for Initial Treatment of FIGO Stages IB3 and IIA2 Cervical Cancer

BACKGROUND Large cancer lesions are often challenging to treat with surgical intervention alone. Neoadjuvant chemotherapy is frequently used for FIGO stage IB3 and IIA2 cervical cancers to optimize the outcomes of radical surgeries. This study aimed to compare the effectiveness of neoadjuvant chemotherapy, followed by adjuvant chemotherapy and radiotherapy, if necessary, with the traditional approach of adjuvant chemotherapy and radiotherapy after radical hysterectomy in treatment-naïve patients with cervical cancer of specified stages. MATERIAL AND METHODS A total of 245 female patients were administered either 70 to 85 mg/m² cisplatin and 165 to 175 mg/m² paclitaxel every 21 days (2 cycles) prior to radical hysterectomy, followed by adjuvant chemotherapy and radiotherapy if needed (neoadjuvant therapy, NT cohort, n=105), or received adjuvant chemotherapy and radiotherapy after radical hysterectomy adjuvant therapy, AT cohort, n=140). RESULTS In the NT cohort, 76% of patients responded to neoadjuvant chemotherapy, while 24% did not. Adverse operative, intraoperative, and postoperative outcomes were significantly more common among the non-responders (P<0.05). After 5 years, 91% of responders and 72% of non-responders survived without recurrence (P=0.0372), and 3% of responders and 28% of non-responders had died (P=0.0005). CONCLUSIONS The resistance to neoadjuvant chemotherapy is a poor prognostic factor. Neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant chemotherapy/radiotherapy appears to be advantageous for cervical cancer patients who respond well to neoadjuvant chemotherapy.

A Tumor‐Targeted tRF Therapeutics Triggers Ovarian Cancer Ferroptosis via Dual Inhibition of System Xc −

ABSTRACT The severe chemoresistance‐caused high recurrence has made ovarian cancer (OVCA) the most lethal gynecological malignancy in clinical practice. Ferroptosis represents a promising therapeutic approach for OVCA, which could effectively overcome tumor resistance. Nevertheless, the traditional ferroptosis inducers lack specificity and selectivity, resulting in poor therapeutic effects. Here, we identified a novel tRNA‐derived fragment, tRF‐21‐XSXMSL73E (tRF‐21), which could serve as a ferroptosis inducer to efficiently suppress OVCA growth through dual inhibition of the system Xc − /glutathione (GSH)/peroxidase 4 (GPX4) axis without causing obvious side effects. Mechanistically, tRF‐21 promotes SLC3A2 ubiquitination via SPOP E3 ligase and destabilizes SLC7A11 mRNA by disrupting NSUN2‐mediated m 5 C methylation. This dual‐inhibition effect on the system Xc − /GSH/GPX4 axis leads to GSH depletion, reactive oxygen species (ROS) accumulation, and ferroptotic cell death. To enhance therapeutic delivery, we engineered a pH‐responsive nanoplatform (tRF‐21@EPH) with an ellagic acid core, polyetherimide (PEI) intermediate layer, and hyaluronic acid shell, enabling nuclease protection and tumor‐specific uptake. This system markedly improved tRF‐21 efficacy with minimal toxicity, providing a novel RNA‐based strategy for OVCA treatment.