Proceedings of Anticancer Research

Zorifertinib for EGFR-mutant Non-small Cell Lung Cancer after Leptomeningeal Metastasis on Double-Dose Third-generation EGFR-TKI: A Case Report and Literature Review

2025-10-11T12:40:11+08:00

Background: Leptomeningeal metastasis (LM) after third-generation EGFR-TKIs resistance carries a dismal prognosis. Limited blood–brain-barrier penetration rather than secondary EGFR mutations is the dominant resistance mechanism. We report a case managed with CNS-penetrant EGFR inhibition of zorifertinib. Method: A 53-year-old, never-smoking woman with EGFR L858R-mutant stage IVb non-small-cell lung cancer (NSCLC) developed LM after progression on osimertinib 160 mg and firmonertinib 160 mg. Salvage therapy with zorifertinib (200 mg BID) plus firmonertinib (80 mg qd) was initiated. Results: Within 14 days, the coma resolved. Karnofsky Performance Status improved from 20 to 70. Serial imaging at 3 and 5 months revealed stable disease with shrinkage according to RECIST 1.1. Only grade 1–2 diarrhea, rash, and transaminitis occurred and resolved with symptomatic care. Conclusion: The combination of zorifertinib plus firmonertinib provides durable intracranial control and rapid neurological recovery after third-generation EGFR-TKI failure. Prospective validation is warranted.

Key Driving Pathways and Regulatory Mechanisms of Malignant Transformation of Mammary Gland Epithelial Cells under Long-Term Psychological Stress

2025-10-16T13:57:17+08:00

Objective: This study primarily focuses on analyzing the inductive effects of emotional disturbances on the malignant transformation process of mammary gland epithelial cells. Methods: A total of 42 patients with malignant transformation of mammary gland epithelial cells (breast cancer, observation group) and 42 patients without malignant transformation of mammary gland epithelial cells (non-breast tumors, control group) were selected as research subjects. The earliest consultation time was January 2022, and the latest was January 2024. The extent of psychological stress impact on these patients was compared. Results: Compared with the control group, the observation group experienced a higher frequency and intensity (LEU value) of adverse life events, with P < 0.05. The intensity of adverse life events in the observation group, except for mild events, was significantly higher than that in the control group (P < 0.05). In terms of the content distribution of adverse life events, the proportion of marital and family problems in the observation group was significantly higher than that in the control group (P < 0.05). The negative coping score and positive coping score in the observation group were significantly different from those in the control group (P < 0.05). Regarding social support, the objective support score in the observation group was higher than that in the control group (P < 0.05). Conclusion: During the malignant transformation process of mammary gland epithelial cells, long-term emotional disturbances have a significant impact, indicating a close relationship between psychological stress and the occurrence of breast cancer.

Thyroid Hormones in Prostate Cancer: A Systematic Review and Bibliometric Study

2025-10-16T13:57:04+08:00

Prostate cancer (PCa) is a prevalent malignancy in men, traditionally linked to androgen receptor signaling. Emerging evidence suggests thyroid hormones (THs, particularly T3/T4) play a complex role in PCa biology. THs regulate gene transcription via nuclear receptors TRα/β, modulating proliferation, apoptosis, and AR signaling, while non-genomic pathways through integrin αvβ3 activate MAPK/PI3K–Akt signaling, driving metabolic reprogramming, migration, and angiogenesis. Local DIO enzymes fine-tune T3/T4 levels, with DIO2 enhancing proliferation and DIO3 creating a low-TH microenvironment to facilitate immune evasion. Epidemiological studies associate hyperthyroidism or low TSH with elevated PCa risk, whereas experimental models show inconsistent effects, reflecting regulation by hormone levels, receptor distribution, and tumor molecular features. Bibliometric analyses reveal a shift from epidemiological studies to molecular, immune, and metabolic mechanistic research, though clinical translation remains limited. This review synthesizes current knowledge on THs in PCa, highlighting mechanistic insights, evidence gaps, and future directions, aiming to inform early detection, stratification, and therapeutic strategies.

Exploring the Molecular and Immune Mechanisms Linking Hypothyroidism to Hepatocellular Carcinoma

2025-10-16T13:56:58+08:00

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide, and endocrine, metabolic, and immune factors influence its occurrence and progression. Hypothyroidism (HT) is a common endocrine disorder that may affect cancer risk; however, its relationship with HCC remains unclear. Objective: This study aimed to investigate the potential molecular and immune mechanisms underlying the association between HT and HCC, with a focus on the regulatory effects of HT-related genetic variants on the hepatic tumor immune microenvironment. Methods: Single-nucleotide polymorphisms (SNPs) associated with HT and HCC identified through Mendelian randomization were functionally annotated using the Ensembl Genome Browser and mapped to candidate genes. Functional enrichment and pathway analyses were performed with Metascape. Differentially expressed target genes between HCC and normal liver tissues were screened using GEPIA2, and their protein expression levels were validated in the Human Protein Atlas (HPA) database. The association between target gene expression and immune cell infiltration was further evaluated using TIMER2.0. Results: A total of 68 candidate genes were analyzed. Enrichment analysis revealed that these genes are involved in IFN-γ–mediated immune responses, PI3K/AKT and RAC1 signaling pathways, and other immune regulatory processes. Among them, HLA-DQA1, HLA-DPB1, HLA-DQA2, and PVT1 showed significant differential expression in HCC. HLA-DQA1, HLA-DPB1, and HLA-DQA2 were positively correlated with CD8⁺ T cells, regulatory T cells (Tregs), and M2 macrophages, suggesting that these genes may exert bidirectional effects on antitumor immunity and immunosuppression. PVT1 may influence the immune microenvironment by regulating myeloid cell recruitment and extracellular matrix remodeling. Conclusion: HLA-DQA1, HLA-DPB1, HLA-DQA2, and PVT1 may reduce the risk of HCC by enhancing IFN-γ–mediated antitumor immunity and modulating key signaling pathways, while also contributing to immune microenvironment remodeling. These findings provide mechanistic insights into the protective effects of HT on HCC and suggest potential targets for immunotherapeutic strategies.

Exploring Gastric Cancer-Related Genes and Clinical Significance Analysis Based on Bioinformatics

2025-10-16T13:57:14+08:00

Objective: Employing bioinformatics methodologies to identify core genes intricately associated with the pathogenesis and progression of gastric cancer, and to evaluate their clinical significance. Method: Gene expression datasets GSE19826 and GSE13911 were acquired from the Gene Expression Omnibus (GEO). Differential gene expression analysis was conducted using GEO2R. Common differentially expressed genes (DEGs) were discerned via Venn diagram analysis on a bioinformatics platform. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), were performed on these overlapping DEGs. A protein-protein interaction (PPI) network was constructed with the STRING database, and central hub genes were identified using Cytoscape software. The expression profiles, prognostic value, and immune infiltration correlations of these key genes were further examined utilizing the GEPIA, Kaplan-Meier plotter, Human Protein Atlas (HPA), and TIMER databases. Results: Analysis revealed 120 commonly differentially expressed genes. These genes were significantly enriched in biological pathways concerning muscle cell cytoskeleton regulation, nutrient absorption, and extracellular matrix receptor interactions. PPI network analysis highlighted 10 core genes, including COL1A1, COL1A2, BGN, THBS2, COL5A2, and TIMP1. These genes exhibited marked upregulation in GC tissues. Statistical evaluation confirmed a significant link between their elevated expression and unfavorable patient outcomes (P < 0.01). Furthermore, immune infiltration assessment indicated a positive correlation between the expression of these genes and macrophage infiltration within the tumor microenvironment, implying their involvement in modulating the immune response in GC, which could affect tumor behavior and clinical progression. Conclusion: The six genes identified may function as diagnostic biomarkers and represent promising therapeutic targets for gastric cancer.

A Narrative Study on the Reconstruction of Life Meaning in Breast Cancer Patients

2025-10-16T13:57:12+08:00

This study, conducted during an internship at the Tumor Hospital of S Province, employs a qualitative research paradigm. The primary research subjects were 11 hospitalized breast cancer patients, with data collected through semi-structured interviews and observation, followed by content analysis. The study aims to explore the disease experiences and life experiences of breast cancer patients, investigating what their illness means to them and whether it has led to a different understanding of the meaning of their lives. The findings reveal that the reconstruction of life meaning among breast cancer patients manifests as “new perceptions of existence, new attitudes toward life, and new life goals.”

Integrating Iron Overload Diagnosis with Electrocardiographic Abnormalities: Bridging Laboratory Findings to Primary Care Practice

2025-10-16T13:57:00+08:00

Objective: To investigate the diagnostic status and electrocardiographic correlates in patients with biochemical evidence of iron overload. Methods: We conducted a retrospective cohort study of patients in our hospital with ferritin levels exceeding 500 ng/mL between January 1, 2011, and October 24, 2022 (corresponding to the pre-COVID-19 pandemic period in Beijing). Using ICD-10-CM coded medical records, we assessed the following: definitive diagnostic characterization (genetic or acquired), electrocardiographic (ECG) completion rates, and the prevalence of ECG abnormalities. Statistical analyses, encompassing chi-square tests and correlation studies, were performed using SPSS Statistics software (version 27.0). Results: Except for cases of malignancy, infectious diseases, hematological diseases, chronic diseases, for the unexplained diagnosis group found elevated ferritin during annual health checkup, there were 17 cases in the group with ferritin above 1,000 ng/ml and 36 cases in the group with ferritin ranging from 500 to 1,000 ng/ml, accounting for 23.2% and 25.8% of the entire ferritin analysis respectively, and the total proportion in the entire analysis was 24.0%. Among the cases indicating ferritin higher than 500ng/ml, 24.0% of the cases were of unknown diagnosis. ECG acquisition rate for was 55.7%, with 24% demonstrating abnormalities, including atrial fibrillation, sinus tachycardia arrhythmia, atrioventricular block, prolonged QT interval, T-wave inversion, and ST-segment depression. Conclusion: The study revealed that the proportion of unexplained diagnoses of ferritin overload remains relatively high, and the analysis of the ECG is also insufficient. There is a need to enhance clinicians’ awareness and attention to iron overload in both diagnosis and ECG analysis.

Comparative Study on the Diagnosis of Thoracic Wall and Rib Involvement in Lung Adenocarcinoma Using 99mTc-MDP SPECT/CT and MSCT

2025-10-16T13:56:56+08:00

Objective: To compare the diagnostic value of ^99mTc-MDP SPECT/CT and MSCT in detecting thoracic wall and rib involvement in lung adenocarcinoma. Methods: A retrospective analysis was conducted on the imaging data of 78 thoracic wall and rib lesions from 66 patients, a total of 32 males and 34 females, aged (53.2 ± 5.6) years old with pathologically confirmed lung adenocarcinoma who underwent both ^99mTc-MDP SPECT/CT and MSCT examinations from March 2017 to September 2023. The diagnostic efficacy of the two imaging modalities was compared using pathological confirmation or clinical follow-up as the gold standard. Results: Pathological confirmation or clinical follow-up revealed 74 lesions with thoracic wall bone involvement in lung adenocarcinoma (20 lesions confirmed by surgical pathology and 54 lesions confirmed by clinical follow-up) and 4 lesions without thoracic wall or rib involvement (2 lesions confirmed by surgical pathology and 2 lesions confirmed by clinical follow-up). The diagnostic sensitivity, specificity, and accuracy of ^99mTc-MDP SPECT/CT were 97.3%, 50.0%, and 94.9%, respectively. Its diagnostic sensitivity and accuracy were higher than those of MSCT (72.3% and 74.4%, respectively), with statistically significant differences (P < 0.05). The specificity of ^99mTc-MDP SPECT/CT was lower than that of MSCT (100.0%), but the difference was not statistically significant (P < 0.05). There were no statistically significant differences in the positive predictive value and negative predictive value between ^99mTc-MDP SPECT/CT and MSCT (P > 0.05). ^99mTc-MDP SPECT/CT examination revised the MSCT tumor staging in 14 patients [21.2% (14/66)] with lung adenocarcinoma. Conclusion: ^99mTc-MDP SPECT/CT imaging demonstrates superior diagnostic efficacy compared to MSCT in detecting thoracic wall and rib involvement in lung adenocarcinoma. It offers more accurate tumor staging than MSCT, and an accurate diagnosis aids in clinical treatment decision-making.

Data Mining-Driven: Identification of Potential Traditional Chinese Medicine Categories Targeting Vasculogenic Mimicry in Esophageal Cancer

2025-10-16T13:57:08+08:00

Background: Vasculogenic mimicry refers to a specialized tumor microvasculature independently formed by tumor cells, which facilitates the recurrence, metastasis, and therapeutic resistance in esophageal cancer. Within the framework of traditional Chinese medicine (TCM) theory, there is currently no clear conceptual classification or diagnostic-therapeutic principles for this phenomenon. Objective: To explore traditional Chinese medicine (TCM) herbs and syndrome factors related to the treatment of vasculogenic mimicry in esophageal cancer, and to provide a reference for clarifying the TCM clinical syndromes of vasculogenic mimicry in esophageal cancer. Methods: Based on public databases such as TCMSP, CNKI, and PubMed, TCM herbs related to esophageal cancer, clinical medications, and herbs inhibiting vasculogenic mimicry were retrieved. The herbs collected from multiple databases were standardized, collated, and cross-analyzed, and core herbs were screened for further analysis. Results: Among the public databases, herbs inhibiting vasculogenic mimicry and commonly used clinical herbs for esophageal cancer were mainly of the blood-activating and stasis-resolving type (Huoxue Huayu). In contrast, esophageal cancer-related herbs in the TCMSP database were mainly of the heat-clearing and toxin-resolving type (Qingre Jiedu). A total of 22 TCM herbs related to vasculogenic mimicry in esophageal cancer were identified, mainly blood-activating and stasis-resolving herbs, involving three syndrome factors: “blood stasis (Xueyu), Qi deficiency (Qixu), and Qi stagnation (Qizhi).” Conclusion: Vasculogenic mimicry can promote the progression of esophageal cancer, and blood-activating and stasis-resolving herbs may improve the prognosis of patients with esophageal cancer.

Global Research Trends and Hotspots of Contrast- Enhanced Ultrasound in Tumor Diagnosis: A Bibliometric Analysis (2000–2025)

2025-10-20T16:28:16+08:00

Objective: To systematically evaluate global research trends on contrast-enhanced ultrasound (CEUS) in tumor diagnosis using bibliometric methods. Methods: Publications from January 2000 to June 2025 were retrieved from the Web of Science Core Collection (SCI-EXPANDED). Only English-language articles and reviews were included. A total of 3,493 records were analyzed. VOSviewer 1.6.20 were used for bibliometric and visualization analyses, covering annual output, countries and institutions, authors, journals, keyword co-occurrence, collaboration networks, and co-citation patterns. Results: The number of publications demonstrated steady growth with acceleration after 2018, peaking in 2021 and 2023 (> 350 papers/year). Dietrich Christoph F. was the most productive and influential author, while Chinese scholars (e.g., Dong Yi, Wang Wen-Ping) and institutions such as Sun Yat-sen University and Fudan University emerged as leading contributors. European journals, particularly Ultrasound in Medicine and Biology and European Radiology, showed high academic influence. Keyword analysis revealed liver cancer, especially hepatocellular carcinoma, as the dominant research theme, with expanding applications in breast, renal, and prostate tumors. Collaboration networks highlighted strong partnerships between China and Europe, whereas North American participation remained limited. Co-citation analysis indicated that a small number of highly cited studies shaped the intellectual foundation of the field. Conclusion: CEUS research in tumor diagnosis has expanded rapidly, characterized by concentrated leadership, thematic diversification, and strengthening international collaboration. With advances in artificial intelligence, super-resolution imaging, and novel contrast agents, CEUS is expected to evolve from a diagnostic tool into an integrated platform for tumor detection, treatment monitoring, and personalized cancer care.

Synergistic Potential of Traditional Chinese Medicine and CART Cell Therapy: Immunoenhancement and Persistence Regulation Strategies

2025-10-16T13:57:10+08:00

CAR-T cell therapy demonstrates tremendous potential for tumor treatment, yet faces challenges in solid tumor therapy due to immune suppression, T-cell exhaustion, and cytokine release syndrome (CRS) induced by the tumor microenvironment (TME). Traditional Chinese medicine (TCM) holds substantial potential to enhance CAR-T efficacy and mitigate adverse reactions due to its multi-targeted advantages. TCM active ingredients and formulations can synergistically amplify CAR-T anti-tumor effects while reducing adverse events through multiple mechanisms, including reversing T-cell exhaustion, prolonging CAR-T cell persistence, improving TME hypoxia and fibrosis, modulating gut microbiota, and suppressing CRS. This benefits patient treatment and recovery. Combining TCM with CAR-T therapy can increase objective response rates, prolong cell persistence, and reduce CRS incidence. Future efforts will focus on exploring the precise mechanisms and standardized protocols for TCM-enhanced CAR-T treatment through high-quality clinical trials and multi-omics technologies, driving its clinical translation and application.

Current Status and Prospects of Diagnosis and Intervention for HR-HPV Persistent Infection

2025-10-16T13:57:06+08:00

Persistent infection with high-risk human papillomavirus (HR-HPV) is the core pathogenic factor of cervical cancer (CC). Although HPV vaccination is an effective primary prevention method for CC, the global vaccination rate is generally insufficient (target population vaccination rate in China < 5%), far from meeting the requirements for herd immunity (80%) and the WHO target (90%). However, only about 10% of HR-HPV infections progress to persistent infections. Therefore, identifying and intervening in the “HR-HPV persistent infection” population can systematically narrow the scope of prevention and control, reduce prevention and control costs, and provide a new path for low-income countries to explore suitable prevention and control models for CC. Based on this understanding, the team has pioneered a systematic method for identifying HR-HPV persistent infections and a tiered intervention system based on drug classification, which has achieved good results in both basic research and clinical observations. This article will summarize the current research status of “HR-HPV persistent infection” in relation to CIN and CC, as well as the team’s relevant concepts and research results, to provide a reference for the identification and intervention of “HR-HPV persistent infection.”

Revisiting IL-1 Antagonism in Lung Cancer Therapeutics: Lessons from Failure and Pathways to Precision Therapy

2025-10-16T13:57:02+08:00

Despite compelling preclinical and epidemiological evidence (e.g., reduced lung cancer incidence in the CANTOS trial), IL-1β inhibition with canakinumab failed to achieve the expected therapeutic effect in the Phase III clinical trials (CANOPY series) of non-small cell lung cancer (NSCLC). This perspective analyzes the disconnect between mechanistic promise and clinical outcomes. IL-1β drives NSCLC progression by promoting immunosuppression, angiogenesis, and metastasis. However, CANOPY-2 showed no overall survival (OS) benefit, though a trend emerged in patients with an elevated baseline of high-sensitivity C-reactive protein (hs-CRP). Similarly, CANOPY-1 and adjuvant CANOPY-A missed primary endpoints for progression-free survival (PFS) and disease-free survival (DFS), respectively. These failures highlight limitations of IL-1 monotherapy in advanced, immunosuppressive microenvironments and underscore inadequate patient selection. We propose that IL-1 antagonism retains therapeutic potential but requires refined strategies: biomarker-driven enrichment (e.g., inflammation signatures like hs-CRP), rational combinatorial regimens informed by successful multi-target agents (e.g., cadonilimab), and early-stage intervention. Repositioning IL-1 blockers through precision approaches could unlock their value in immuno-oncology.