Anti-Cancer Drugs最新文献

{"title":"VTCN1 emerges as a biomarker of immune tolerance in osimertinib-resistant lung cancer.","authors":"Lifang Wang, Jingjie Liu, Bin Shi","doi":"10.1097/CAD.0000000000001753","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001753","url":null,"abstract":"<p><p>Osimertinib is an effective strategy for nonsmall-cell lung cancer (NSCLC). However, the acquired resistance neutralizes the efficacy of osimertinib. Herein, we investigated the potential biomarkers of osimertinib-resistant lung cancer. GSE200894 was used to analyze the differentially expressed genes in osimertinib-resistant lung cancer. Sixty-two paired surgical specimens were collected from NSCLC patients with stage I-IV. Gene expression was detected using reverse transcription (RT)-qPCR, western blot, and immunohistochemistry. V-set domain containing T cell activation inhibitor 1 (VTCN1) was overexpressed in osimertinib-resistant lung cancer. High levels of VTCN1 predicted advanced stages and distant metastasis. Moreover, VTCN1 expression was negatively correlated with the purity of CD8+ T cells in lung cancer patients. VTCN1 inhibits the infiltration of effector-memory CD8+ T cells. In addition, overexpressed VTCN1 predicted the exhaustion of CD8+ T cells. VTCN1 inhibits the tumor-killing ability of CD8+ T cells. In summary, VTCN1 is overexpressed in osimertinib-resistant lung cancer patients. High levels of VTCN1 confer to inhibition of CD8+ T cell immunity and immune tolerance in osimertinib-resistant lung cancer patients.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming refractory leptomeningeal metastasis in nonsmall cell lung cancer with intrathecal pemetrexed and osimertinib: a case report.","authors":"Li Xue, Xuhui Zhao, Xiaohui Tai, XuXia Zhang, Lingfang Zhang, Hongling Li","doi":"10.1097/CAD.0000000000001748","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001748","url":null,"abstract":"<p><p>Leptomeningeal metastasis (LM), a devastating complication of advanced nonsmall cell lung cancer (NSCLC), severely compromises patient survival and quality of life. Currently, standardized diagnostic criteria and treatment protocols for NSCLC-associated LM remain undefined, posing significant clinical challenges. Here, we present a case of a 58-year-old female with advanced epidermal growth factor receptor (EGFR)-mutated (exon 19 deletion) lung adenocarcinoma who developed LM after failing first-line gefitinib therapy. Initial treatment with osimertinib (80 mg/day), a third-generation EGFR-tyrosine kinase inhibitor (TKI), achieved 8 months of disease control before LM progression. Cerebrospinal fluid genomic analysis revealed acquired EGFR mutations (exon19 L747-A750delins and exon18 L718Q). Combination therapy with intrathecal pemetrexed and standard-dose osimertinib temporarily alleviated neurological symptoms. Upon disease recurrence after 6 months, therapeutic intensification through increased intrathecal pemetrexed frequency and high-dose osimertinib (160 mg/day) resulted in sustained neurological improvement and prolonged survival with manageable toxicity. This case demonstrates the potential of optimized intrathecal/systemic TKI combination strategies for EGFR-mutant NSCLC with LM, providing clinical insights for this therapeutic dilemma.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined amlexanox and anti-MCP-1 therapy suppresses tumor progression in a murine Lewis lung carcinoma model.","authors":"Xiaodan Liu, Xue Dong, Jiaona Wei, Jingxuan Tian, Yuejiao Han, Honglin Li","doi":"10.1097/CAD.0000000000001751","DOIUrl":"10.1097/CAD.0000000000001751","url":null,"abstract":"<p><p>This study aims to assess the effects of combined amlexanox and an antimonocyte chemoattractant protein-1 (MCP-1) mAb therapy in a murine Lewis lung carcinoma (LLC) model. A subcutaneous LLC model was established in mice, which were allocated to either a control group or an intervention group receiving combined amlexanox and anti-MCP-1 mAb. Tumor size was monitored regularly. Immunofluorescence staining was performed to detect MCP-1 and Ki67 expression. Western blot analysis was conducted to assess the expression of TANK-binding kinase 1 (TBK1), macrophage polarization markers (iNOS and arginase-1), and apoptosis-related proteins (MCL-1, Bcl-xL, and Bcl-2). Flow cytometry was employed to quantify macrophage phenotype distributions. TBK1 expression was significantly elevated in LLC tumor tissues. MCP-1 was found to colocalize with the M2 macrophage marker CD206. The combination therapy resulted in a significant reduction in Ki67 expression. arginase-1 expression decreased significantly, while iNOS expression indicated an upward trend, though the change was not statistically significant. Levels of the antiapoptotic proteins MCL-1 and Bcl-xL were significantly downregulated ( P < 0.05), whereas Bcl-2 levels did not differ significantly from those in the control group ( P > 0.05). Flow cytometric analysis indicated a significant decrease in M2 macrophages (F4/80+CD206+) in the intervention group, with no substantial change observed in the proportion of M1 macrophages (F4/80+CD86+). Combined administration of amlexanox and anti-MCP-1 mAb inhibited tumor cell proliferation, promoted apoptosis, and reduced infiltration of tumor-associated M2 macrophages, thereby contributing to suppression of tumor progression in the LLC murine model.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of side effects of anti-EGFR treatments in patients with metastatic colorectal cancer and evaluation of their relationship with survival.","authors":"Mert Erciyestepe, Okan Aydin, Sermin Dinc Sonusen, Ahmet Emin Ozturk, Emir Celik, Muhammed Mustafa Atci, Kayhan Erturk","doi":"10.1097/CAD.0000000000001755","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001755","url":null,"abstract":"<p><p>Many previous studies have investigated cetuximab and panitumumab's efficacy, safety, and side effects. Only a few studies have evaluated the relationship between toxicity and survival. Therefore, we conducted this study to examine the relationship between the side effects of anti-EGFR agents and survival in metastatic colorectal cancer patients. Our study is a single-center retrospective analysis of the medical records of 100 metastatic colorectal cancer patients between September 2014 and September 2023. Overall survival (OS) was found to be statistically significantly longer in patients who developed skin toxicity during anti-EGFR treatment (26.0 vs. 70.0 months) (P < 0.001). Similarly, OS was significantly better in patients with hypomagnesemia (P < 0.001) and constipation (P < 0.001) side effects. In contrast, OS was significantly worse in patients with lung toxicity (P = 0.016). Ocular side effects during anti-EGFR treatment did not affect OS statistically significantly (P = 0.268). The median PFS of patients with skin toxicity with anti-EGFR agents and hypomagnesemia in first-line treatment was 22.0 months (19.4-24.5) and 21.0 months (18.2-23.8), respectively (P = 0.002, P = 0.022). In the second line, the median PFS of patients with skin toxicity and patients with hypomagnesemia who received anti-EGFR therapy was 19.0 months (6.2-31.8) and 17.0 months (8.4-25.6), respectively (P = 0.013, P = 0.037). In our study, it was found that skin toxicity and hypomagnesemia positively affected both OS and PFS. OS was longer in patients with constipation, and OS was shorter in patients with lung toxicity. We suggest that survival might be predicted by monitoring side effects of these therapeutics; therefore, studies with larger cohorts are required.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-line lorlatinib treatment in a 19-year-old patient with ALK-rearranged pulmonary large-cell neuroendocrine carcinoma: a case report and literature review.","authors":"Fatih Kemik, Pinar Bulutay, Cevat İlteriş Kikili, Bahadir Köylü, Nazan Demir, Elif Değirmenci, Kadir Burak Özer, Çisel Aydin Meriçöz, Serhan Tanju, Fatih Selçukbiricik","doi":"10.1097/CAD.0000000000001754","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001754","url":null,"abstract":"<p><p>Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive subtype of nonsmall cell lung cancer, typically occurring in elderly male smokers. Its occurrence in the adolescent population is exceptionally uncommon, with only a handful of cases reported in the literature. Even more rarely, LCNEC harbors ALK fusions, an unusual molecular alteration with important therapeutic relevance. We report a 19-year-old female patient who presented with bone pain and was found to have widespread skeletal and mediastinal lymph node involvement. Initial workup revealed elevated serum calcitonin and carcinoembryonic antigen (CEA) levels, and histopathology showed high-grade neuroendocrine carcinoma with immunoreactivity for chromogranin, synaptophysin, CD56, as well as calcitonin and CEA. Due to the neuroendocrine phenotype and calcitonin positivity, metastatic medullary thyroid carcinoma was initially suspected. However, thyroid fine needle aspiration from the suspicious thyroid nodule did not provide any evidence in this direction, and the RET mutation testing was also negative. Further molecular analysis revealed an EML4-ALK fusion and a TP53 mutation in tumor tissue. The patient was diagnosed with ALK-positive LCNEC and treated with lorlatinib and denosumab combination. A marked clinical and metabolic response was achieved within 3 months of treatment initiation. To our knowledge, this is the first reported case of ALK-rearranged pulmonary LCNEC in an adolescent patient treated with a tyrosine kinase inhibitor. This case underscores the extreme rarity of LCNEC in adolescents, highlighting that ALK rearrangements, although exceptionally rare in this histological subtype, can have significant therapeutic implications. It further emphasizes the importance of routine molecular profiling in atypical clinical scenarios and supports the utility of targeted therapies in rare tumor subsets.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mTOR pathway inhibition with everolimus in pseudomyogenic hemangioendothelioma harboring SERPINE1-FOSB gene fusion: a case report and review of the literature.","authors":"Cevat İlteriş Kikili, Bahadir Köylü, Fatih Kemik, Nazan Demir, Mehmet Ali Deveci, Fatih Selçukbiricik","doi":"10.1097/CAD.0000000000001752","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001752","url":null,"abstract":"<p><p>Pseudomyogenic hemangioendothelioma (PHE) is an extremely rare tumor that is frequently misdiagnosed as other vascular or soft tissue neoplasms and typically follows an indolent course. Due to its locally aggressive and multifocal nature, surgical intervention is often not feasible. Moreover, conventional chemotherapy has shown limited efficacy according to existing literature. Recent advances in genetic profiling have identified a SERPINE1/FOSB gene fusion in PHE, leading to the activation of the mechanistic target of rapamycin (mTOR) pathway. This discovery has highlighted mTOR inhibitors and multityrosine kinase inhibitors as promising therapeutic options. In this report, we present a PHE case with confirmed SERPINE1/FOSB fusion who was initiated on everolimus therapy, along with a review of the current literature.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to PARP inhibitor in EGFR-tyrosine kinase inhibitor-resistant metastatic lung adenocarcinoma with germline PALB2 mutation.","authors":"Chao Zhu, Peng Xu, Lantao Li, Hongmei Wei","doi":"10.1097/CAD.0000000000001712","DOIUrl":"10.1097/CAD.0000000000001712","url":null,"abstract":"<p><p>Tumors with homologous recombination deficiency (HRD) can benefit from treatment with poly ADP-ribose polymerase inhibitors (PARPi). However, the methods for identifying HRD vary and are controversial. Several DNA repair genes in the homologous recombination repair pathway may be linked to PARPi susceptibility, and studies are underway to identify biomarkers that can predict the response to PARPi. We present a case of EGFR-tyrosine kinase inhibitor-resistant metastatic lung adenocarcinoma with a germline PALB2 mutation that was treated with fluzoparib (an orally administered PARPi). The treatment achieved surprising results and lasted for more than 4.5 months. Our study provided evidence that metastatic lung adenocarcinoma with germline PALB2 could benefit from PARPi, which improves patient outcomes.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"518-520"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombospondin-2 induces M2 macrophage polarization through fatty acid metabolism to drive lung adenocarcinoma proliferation.","authors":"Meiling Weng, Xiaoping Zhu","doi":"10.1097/CAD.0000000000001713","DOIUrl":"10.1097/CAD.0000000000001713","url":null,"abstract":"<p><p>Tumor-associated macrophages play a critical role in regulating the progression of lung adenocarcinoma (LUAD). Platelet-derived protein thrombospondin-2 (THBS2) has been identified as a tumor marker and is known to be overexpressed in LUAD. However, the specific role of THBS2 in M2 macrophage polarization within LUAD remains unclear. We conducted bioinformatics analyses to assess the clinical significance of THBS2 expression in LUAD, which was subsequently validated using quantitative PCR. We examined the relationship between THBS2 expression and M2 macrophage infiltration. A coculture system of LUAD cells and M0 macrophages was established to investigate the influence of THBS2 on macrophage infiltration and polarization through immunofluorescence and ELISA. We explored the impact of THBS2 on fatty acid metabolism (FAM) using oil red O staining and relevant kits and elucidated the role of THBS2 in regulating M2 macrophage polarization and LUAD proliferation through cell counting kit-8 (CCK-8) and colony formation assays. Western blot was employed to assess expression changes of Bax and Bcl-2. THBS2 was highly expressed in LUAD and was associated with poor prognosis in patients. In-vitro experiments demonstrated that silencing THBS2 significantly inhibited macrophage infiltration and polarization. THBS2 primarily activated FAM pathways, inducing M2 macrophage polarization and promoting LUAD cell proliferation. THBS2 enhanced LUAD proliferation by regulating FAM to induce M2 macrophage polarization. These findings provide a theoretical basis for targeting THBS2 as a novel therapeutic strategy in LUAD.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"459-467"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlative analysis of immune-related thyroid dysfunction and prognosis in patients with advanced esophageal squamous cell carcinoma.","authors":"Liangshan Da, Ziting Qu, Yiyin Zhang, Jie Da, Kangsheng Gu","doi":"10.1097/CAD.0000000000001716","DOIUrl":"10.1097/CAD.0000000000001716","url":null,"abstract":"<p><p>To explore the clinical characteristics of immune-related thyroid dysfunction (TD) and its correlation with prognosis. By collecting the clinical data of 116 patients with advanced esophageal squamous cell carcinoma (ESCC) who received programmed death receptor-1 (PD-1) inhibitor treatment, we analyzed the clinical characteristics of immune-related TD and its influencing factors and compared the prognostic differences among patients in different groups. Immune-related TD occurred in 45 (38.8%) patients after PD-1 inhibitor treatment, and the median time to its occurrence was 11.3 weeks. The toxicity of immune-related TD was grade 1 or grade 2 and only required symptomatic treatment. Female patients, as well as those with an Eastern Cooperative Oncology Group Performance Status less than equal to 1, no lymph node metastasis, no history of drinking, and high baseline thyroid-stimulating hormone levels, were likely to develop immune-related TD. Compared with the patients in the group without immune-related TD [TD(-)], the median progression-free survival (mPFS) and median overall survival (mOS) of the patients in the immune-related TD [TD(+)] group were significantly prolonged (mPFS: 12.6 vs. 6.5 months, P  = 0.001; mOS: 20.2 vs. 11.2 months, P  < 0.001). Further subgroup analysis showed that compared with the patients in the group without immune-related overt TD (Overt_TD), the patients in the Overt_TD group had a longer PFS (mPFS: 12.4 vs. 7.3 months, P  = 0.015) and OS (mOS: 20.2 vs. 12.2 months, P  = 0.001). The 60-, 90-, and 120-day landmark analysis further confirmed that immune-related TD was significantly associated with the improvement of PFS and OS. Multivariate Cox regression analysis indicated that immune-related TD was an independent prognostic factor for PFS ( P  = 0.015) and OS ( P  = 0.004). Immune-related TD is a very common immune-related adverse event. It is safe and manageable and has potential prognostic value for patients with advanced ESCC treated with PD-1 inhibitors.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"501-508"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transformation from acquired EGFR 19del/C797S to EGFR 19del/T790M in an advanced non-small cell lung cancer patient: a case report and literature review.","authors":"Xianhuai Jin, Yaping Quan, Jiao Liu, Yong Hu, Hao Li","doi":"10.1097/CAD.0000000000001707","DOIUrl":"10.1097/CAD.0000000000001707","url":null,"abstract":"<p><p>Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the first-line treatment of choice for patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, patients treated with these inhibitors eventually develop resistance. One of the most common mechanisms is the emergence of the EGFR C797S mutation. Whether first-generation EGFR inhibitors (e.g. icotinib or gefitinib) can sustainably control EGFR-sensitive mutations/C797S NSCLC following third-generation EGFR inhibitor treatment remains insufficiently reported. Our case report discusses a female patient with advanced lung adenocarcinoma carrying an EGFR exon 19 E746_A750delELREA mutation who received almonertinib as first-line treatment and developed C797S resistance during therapy. The patient was subsequently treated with a double dose of icotinib for 8 months until disease progression occurred, along with the development of an EGFR exon 20 T790M point mutation and TP53 mutation. This case provides clinical evidence suggesting that first-generation EGFR-TKIs may be an effective treatment strategy for patients with acquired EGFR 19del/C797S resistance following EGFR TKI therapy.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"513-517"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}