Multiplex immunofluorescence staining demonstrated that BCL-xL inhibition effectively triggered apoptosis in heterogeneous PDX tumor slice models, including models harboring oncogenic BRAF mutations. Our findings suggest that cetuximab-resistant CRC retains apoptotic competence, and that BCL-xL inhibition serves as a robust alternative therapeutic strategy that is largely independent of the tumor mutational profile.

P2, N=33, Active, not recruiting, Fundación GECP | Trial primary completion date: Nov 2025 --> Nov 2026

P2, N=50, Completed, Yale University | Active, not recruiting --> Completed

P=N/A, N=22, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

CS4 showed the highest immune infiltration, elevated tumor mutational burden, and enhanced sensitivity to 5-fluorouracil and cetuximab. This integrative multi-omics framework refines the molecular taxonomy of COAD, revealing immunologically active and therapeutically distinct subgroups. The classification not only bridges genomic, epigenomic, and transcriptomic regulation but also provides a practical roadmap for precision oncology by linking molecular features to potential treatment strategies.

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.

Furthermore, CD24 knockdown reduced its expression level by promoting the ubiquitination modification of epidermal growth factor receptor (EGFR), and significantly inhibited its downstream AKT/mTOR signaling pathway. By interacting with EGFR and modulating the mTOR pathway, CD24 acted as a critical regulator of autophagic cell death, thereby enhancing the sensitivity of HER2+ BC cells and reversing Pyrotinib resistance.

P1, N=18, Not yet recruiting, M.D. Anderson Cancer Center

P1/2, N=44, Not yet recruiting, Northwestern University | Trial completion date: Jun 2030 --> Jun 2031 | Trial primary completion date: Jun 2030 --> Jun 2031

Threshold analysis established cost-effective pricing thresholds for rezivertinib ($605.02 at 3×GDP per capita, $408.66 at 1.5×GDP per capita). Rezivertinib demonstrates significantly better cost-effectiveness compared to gefitinib for first-line treatment of EGFR-mutated advanced NSCLC in China.

P1/2, N=933, Recruiting, Regeneron Pharmaceuticals | Trial completion date: Dec 2026 --> Apr 2027

P2, N=214, Active, not recruiting, Gruppo Oncologico del Nord-Ovest | Trial completion date: Dec 2025 --> Mar 2026