Collectively, our findings suggest GlcN as a potential therapeutic agent for HCC and underscore its chemosensitizing potential when combined with lenvatinib. Given GlcN's established clinical safety, this combination offers a translatable strategy for HCC therapy.

P=N/A, N=4, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

The cytotoxicity and pro-apoptotic effects were significantly attenuated by the ROS scavenger NAC. These findings provide a solid preclinical foundation for the further development of this combination therapy and underscore the importance of the "computational prediction-mechanistic validation" strategy in advancing cancer drug discovery.

Recent studies indicate that multiple Ubiquitin-Specific Proteases (USP) family members play pivotal roles in lung cancer: Ubiquitin-Specific Peptidase 7 (USP7) promotes proliferation and osimertinib resistance in non-small cell lung cancer by stabilising proteins such as ERβ, c-Abl, and KRAS; Ubiquitin-Specific Peptidase 9, X-linked (USP9X) mediates radiotherapy resistance by regulating KDM4C and REV1; USP10 influences cellular metabolism and chemotherapy sensitivity via PTEN/AKT/mTOR and HDAC6 pathways; Ubiquitin-Specific Peptidase 14 (USP14) enhances tumour migration by regulating β-catenin and Acf7 stability; Ubiquitin-Specific Peptidase 22 (USP22) amplifies tumour stem cell properties and suppresses ferroptosis via EGFR and BMI1 signalling; Ubiquitin-Specific Peptidase 35 (USP35) and Ubiquitin-Specific Peptidase 38 (USP38) respectively modulate apoptosis resistance and proliferation through BIRC3 and KLF5; while Ubiquitin-Specific Peptidase 39 (USP39) influences mitochondrial metabolism via PDHA, thereby promoting tumour growth...It further explores the potential value of small-molecule inhibitors targeting USPs (such as P5091, IU1, and gentiopicroside) in reversing drug resistance, inducing apoptosis, and enhancing immunotherapy...This paper reviews the molecular mechanisms and targeting strategies of USPs in lung cancer based on a systematic literature search of PubMed and Web of Science databases. It further explores their potential applications in precision lung cancer therapy, providing theoretical foundations and directional guidance for future research.

P2, N=47, Not yet recruiting, Sun Yat-sen University

The complementary activity of lirafugratinib and futibatinib against FGFR2 kinase domain mutations supports their sequential use, when precise resistance mutations are detected in patients.

External validation yielded AUCs of 0.922, 0.760, and 0.722 for corresponding time points. The PLANES model was successfully established and validated for predict prognosis in unresectable HCC patients receiving first-line triple therapy.

We also explored clinical phosEGFR reduction induced by the 3rd generation TKI osimertinib, suggesting that limited target engagement may explain modest response achieved in EGFR Exon20Ins at the clinically investigated doses. The developed model is a valuable tool to understand the impact of kinetic characteristics on phosEGFR reduction and related efficacy, select a target engagement-based criterion for therapeutic dose predictions, and provide interpretation and insights on observed clinical efficacy of irreversible inhibitors in EGFR Exon20Ins.

The efficacy of TKIs was consistent across SQC forms (including de novo or adenocarcinoma-transformed cases) and EGFR mutation types. The findings indicate that, compared with early-generation TKIs, third-generation TKIs are effective against de novo SQCs and should be considered a plausible treatment option for transformed SQCs.

P2, N=40, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=64, Not yet recruiting, Chinese University of Hong Kong

P2, N=36, Recruiting, Guangzhou Medical University | Not yet recruiting --> Recruiting | Trial completion date: Mar 2026 --> Mar 2027