Lung cancer is a malignant tumor whose incidence is rapidly increasing worldwide. GLOBOCAN estimated approximately 2.2 million new cases (accounting for 11.4 % of all malignant tumors) and 1.8 million deaths (18.0 %) due to lung cancer worldwide in 2020 [1]. Lung cancer can be classified as non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) based on histopathology. NSCLC is the most common lung cancer type that accounts for approximately 85 % of all lung cancer cases [2]. Treatments for NSCLC primarily include surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. While targeted therapies have improved survival rates for patients with NSCLC, patients harboring specific genetic mutations such as tumor protein 53 (TP53) mutations continue to experience suboptimal therapeutic outcomes [3].

TP53 is a common tumor suppressor gene that encodes the protein p53 and is involved in DNA repair, metabolism, cell cycle arrest, apoptosis, and various developmental processes. During DNA damage or activation of oncogenes, p53 can activate cyclin-dependent kinase (CDK) inhibitor 1 A (CDKN1A) and inhibit CDK complexes, eventually leading to cell cycle arrest [4]. TP53 mutations are associated with the loss of p53 function or gain of a new function that promotes invasion, metastasis, and proliferation of cancer cells [5]. TP53 mutations is high in NSCLC, observed in 35–60 % of all cases [6,7]. Unfortunately, TP53-mutated patients with NSCLC have poorer survival outcomes, compared to wild-type TP53 [8,9].

Anti-angiogenic therapy improves the prognosis of patients with TP53-mutated NSCLC. Vascular endothelial growth factor A (VEGF-A) expression levels are elevated in patients with TP53-mutated NSCLC, and anti-angiogenic drugs can improve progression-free survival (PFS) in these patients [10]. A study showed that three patients with advanced NSCLC with TP53 mutation who had failed previous treatment and received anlotinib achieved a partial response (PR), with PFS reaching 8, 6.5, and 5 months, respectively [11]. This suggests that the use of anti-angiogenic agents may be a strategy for the treatment of TP53-mutated NSCLC.

Anlotinib is a small molecule multi-target tyrosine kinase inhibitor (TKI) that can inhibit vascular endothelial growth factor receptor (VEGFR)-2, VEGFR1, VEGFR3, platelet-derived growth factor receptor-β (PDGFR-β), stem cell growth factor receptor (c-Kit), and achieve an anti-tumor effect [12]. Anlotinib has shown inhibitory effects in clinical studies on multiple solid tumors and has been approved as the late-line treatment for advanced NSCLC, advanced soft tissue sarcoma, advanced SCLC, and advanced medullary thyroid cancer [13]. In clinical practice, anlotinib exerts inhibitory effects on TP53-mutated lung cancer [14,15]. However, the action mechanism of anlotinib in the treatment of TP53-mutated NSCLC remains unclear. In this study, we use label-free quantitative proteomics to identify the differentially represented proteins in TP53-mutated NSCLC cell treated with anlotinib. Proteins associated with the TP53 signaling pathway were identified using bioinformatics methods and verified. This study revealed the potential inhibitory efficacy and action mechanism of anlotinib in TP53-mutated NSCLC cells, suggesting its potential for the clinical treatment of TP53-mutated NSCLC.