Furthermore, through computer-simulated clinical trials, we find that reducing the dose of apatinib in combination therapy to 125 mg can still achieve therapeutic effects comparable to the original dose. These findings provide valuable insights for future drug development and clinical trial design.

P2/3, N=1, Completed, Eli Lilly & Co. | Active, not recruiting --> Completed

P2, N=48, Recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Not yet recruiting --> Recruiting

P3, N=106, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

Eighteen P4-generation PDX mice were randomized into three groups (*n*=6/group): Control: 100 μL/day saline (oral gavage), Cisplatin: 5 mg/Kg/week (intraperitoneal injection), Apatinib: 100 mg/Kg/day (oral gavage). These findings support its potential as a targeted therapy for tongue cancer and highlight the utility of PDX models for preclinical drug evaluation. Further studies with larger cohorts are warranted to validate these results.

P1/2, N=200, Recruiting, UZ Leuven

P2, N=30, Active, not recruiting, First Affiliated Hospital of Zhejiang University | Recruiting --> Active, not recruiting | Trial completion date: Sep 2025 --> Dec 2026

Despite profound genomic instability, targeting DNA repair or replication stress pathways was ineffective, whereas sensitivity to platinum-based chemotherapy was retained across clades. Collectively, these findings indicate that recurrent senescence escape drives osimertinib resistance through widespread genomic instability and is most effectively treated by cytotoxic strategies rather than pathway-targeted approaches.

Here, we found that exosomes secreted by lung cancer cells that had acquired epidermal growth factor receptor tyrosine kinase inhibitor resistance and undergone epithelial-mesenchymal transition (osimertinib- and WZ4002-resistant H1975) exhibited enhanced brain-specific distribution and a concomitant increase in BrM compared with exosomes from parental H1975 cells. Clinically, exosomal L1CAM demonstrated diagnostic potential for BrM (area under the curve [AUC] = 0.80), and a combined exosomal L1CAM/ITGB3 panel significantly improved diagnostic accuracy (AUC = 0.98). Collectively, these findings identify exosomal L1CAM as a key regulator of brain-specific metastasis and support the clinical utility of the L1CAM/ITGB3 panel as a noninvasive biomarker for BrM in lung cancer.

With a primary EGFR p.L858R-mutant NSCLC, osimertinib was administered, resulting in a partial response within 10 months. In addition, given the synchronous primary pancreatic adenocarcinoma, germline testing was performed, revealing a CDKN2A p.I49T variant consistent with melanoma-pancreatic cancer syndrome, prompting comprehensive cancer surveillance and familial testing. This case illustrates how ctDNA testing enabled a comprehensive evaluation by clarifying the diagnosis, identifying actionable biomarkers, and facilitating genetic risk assessment, ultimately having a significant impact on the patient's clinical management.

P2, N=29, Active, not recruiting, Tianjin Medical University Cancer Institute and Hospital | Recruiting --> Active, not recruiting

The translation potential of this scaffold is also supported by the clinical success of indole-based EGFR inhibitors, including the third-generation drug osimertinib. This paper summarizes the relevant literature of indole EGFR inhibitors published between 2021 and 2025, which may include mechanistic insights, biological screening, and therapeutic potential. The indole scaffold can be a useful starting point to push forward the next generation of targeted cancer therapies.