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

Upon ultrasound exposure as an "exogenous switch," activated Ce6, together with Vitamin K3 and Mn2+, induces a robust ROS storm, resulting in mitochondrial dysfunction and immunogenic cell death (ICD), while effectively reprogramming the chronic hypoxia-HIF-2α-driven immunosuppressive tumor microenvironment. Furthermore, in vivo studies demonstrated that Lenvatinib therapy, when combined with the nanoplatform, further suppressed chronic hypoxia-HIF-2α-driven abnormal angiogenesis, enhanced CD8+ T-cell infiltration, and boosted antitumor immune responses, ultimately achieving a potent synergistic therapeutic effect and promoting the conversion of "cold tumors" into "hot tumors." This study provides strong experimental evidence that nanoplatform-mediated immune microenvironment reprogramming represents a precisely controllable and highly effective therapeutic strategy for solid tumors, with promising translational potential in hepatocellular carcinoma.

For classical EGFR mutations such as exon 19 deletion and exon 21 L858R mutation, combination strategies in the first-line setting, based on the results of the MARIPOSA (lazertinib and amivantamab) and FLAURA 2 (platinum-based doublet chemotherapy and osimertinib) trials, provide promising outcomes. Optimising the treatment sequence in advanced EGFR-mutated NSCLC is crucial to ensure the best survival outcomes along with the best treatment tolerance and quality of life. Predictive biomarkers are strongly needed as well as biomarker-based escalation and de-escalation clinical trials.

P=N/A, N=8, Not yet recruiting, Guangdong Second Provincial General Hospital (Guangdong Provincial Emergency Hospital); Guangdong Second Provincial General Hospital (Guangdong Provin

P=N/A, N=120, Not yet recruiting, West China Hospital, Sichuan University; West China Hospital, Sichuan University

P=N/A, N=80, Not yet recruiting, The First Affiliated Hospital of Wenzhou Medical University; The First Affiliated Hospital of Wenzhou Medical University

P=N/A, N=30, Recruiting, The Affiliated Hospital of Xuzhou Medical University; The Affiliated Hospital of Xuzhou Medical University