Anti-Cancer Drugs最新文献

{"title":"Exploring natural products for allosteric inhibition of glutathione peroxidase 4 in drug-resistant cancers via molecular docking and dynamics.","authors":"Mohammad Yasir, Jeevan Patra, Rahul K Maurya, Alok S Tripathi, Hero Khan Pathan","doi":"10.1097/CAD.0000000000001749","DOIUrl":"10.1097/CAD.0000000000001749","url":null,"abstract":"<p><p>Glutathione peroxidase 4 (GPX4) plays a pivotal role in regulating ferroptosis and maintaining redox homeostasis, making it a critical target in drug-resistant cancers. Recent studies suggest that allosteric inhibition of GPX4 could overcome resistance mechanisms. This study aimed to identify natural products with potential allosteric inhibition of GPX4 using computational approaches. A comprehensive virtual screening was conducted on a curated library of 125 415 natural compounds derived from the COlleCtion of Open Natural ProdUcTs (COCONUT) database. Structure-based virtual screening and molecular docking were performed against the allosteric site of GPX4 (PDB ID: 7U4N) using UCSF DOCK6. The top candidates were evaluated through binding free energy calculations [molecular mechanics Poisson-Boltzmann surface area (MM-PBSA)] and 100 ns molecular dynamics simulations using the AMBER20 package. Pharmacokinetic and toxicity profiles were assessed through absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis. Five natural compounds - quercetin, zeatinriboside, ribofuranosylmakaluvic acid C, tecleanatalensine B, and scopolamine - exhibited superior binding affinities (docking scores ranging from -4.01 to -4.95 kcal/mol) compared with the cocrystallized ligand (-3.15 kcal/mol), with significant interactions at the key Cys66 residue of GPX4. MM-PBSA analysis revealed highly favorable binding free energies (up to -37.94 kcal/mol), indicating stable ligand-protein complexes. Molecular dynamic simulations confirmed structural stability, with minimal root mean square deviation and root mean square fluctuations. ADMET profiling suggested favorable solubility, absorption, low toxicity, and good drug-likeness. This study highlights the potential of natural products as allosteric inhibitors of GPX4. The identified compounds demonstrated strong and stable interactions with the GPX4 allosteric site and possessed desirable pharmacokinetic properties, warranting further in-vitro and in-vivo investigations for potential development as anticancer agents targeting drug-resistant cancers.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"723-730"},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473841","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":"Serum heat shock protein family A member 9 protein as a biomarker for bortezomib resistance and poor prognosis in patients with multiple myeloma.","authors":"Lin Chen, Shuang Gao, Li Lin, Su Liu, Jing Ma, Zhiying Zhang, Qian Li","doi":"10.1097/CAD.0000000000001764","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001764","url":null,"abstract":"<p><p>Bortezomib resistance in multiple myeloma (MM) is a significant clinical challenge that limits the long-term effectiveness. Currently, there is a lack of reliable biomarkers to predict bortezomib resistance. Previous studies reported that several proteins regulate bortezomib resistance through targeting ubiquitin-proteasome pathways, including heat shock protein family A member 9 (HSPA9), dickkopf Wnt signaling pathway inhibitor 1 (DKK1), proteasome 26S subunit non-ATPase 14 (PSMD14), and tripartite motif containing 21 (TRIM21). In our study, we aimed to analyze the expression of these proteins in MM patients and evaluate their potential as biomarkers for bortezomib resistance. Our study enrolled 46 newly diagnosed MM patients (38 bortezomib-sensitive and eight bortezomib-resistant patients) and 52 healthy controls, and serum samples were collected from the patients before initial treatments. The levels of HSPA9, DKK1, PSMD14, and TRIM21 proteins in serum samples were measured using ELISA. The diagnostic power of HSPA9 protein for bortezomib resistance was evaluated through receiver operating characteristic curves combined with the area under curve (AUC). The correlation between HSPA9 protein and clinicopathological features was examined using the chi-square test, and Kaplan-Meier method and Cox regression analysis were applied to assess prognostic value. Compared with healthy controls, increased HSPA9 and DKK1, but decreased TRIM21 protein expression, were observed in serum samples from MM patients. There was no statistical difference in PSMD14 protein expression between the two groups. Notably, compared with bortezomib-sensitive patients, only HSPA9 protein was found to be upregulated in bortezomib-resistant patients, whereas no differences were found in the other proteins. Furthermore, the AUC of serum HSPA9 for differentiating MM patients from healthy controls was 0.906 [95% confidence interval (CI): 0.843-0.968]. And serum HSPA9 expression could effectively differentiate bortezomib-resistant MM patients from bortezomib-sensitive MM patients, with an AUC of 0.845 (95% CI: 0.734-0.957). In addition, elevated serum HSPA9 expression positively correlated with advanced International Staging System stage, increased β2-MG, abnormal immunoglobulin, and bortezomib resistance. Higher serum HSPA9 was linked to shorter overall survival rate and independently predicted poor prognosis. Our study demonstrated that elevated serum HSPA9 protein serves as a potential biomarker for bortezomib resistance and poor prognosis in MM patients.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013651","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":"Pembrolizumab treatment in SMARCA4-deficient nonsmall cell lung cancer: high tumor mutational burden and programmed death-ligand 1(+) expression on circulating tumor cells for real-time monitoring: a case report.","authors":"Youjun Deng, Yan Huang, Songhua Cai, Chujian Huang, Wenyi Liu, Ran Jia, Zhilin Sui, Heng Zou, Zhentao Yu, Xiaotong Guo","doi":"10.1097/CAD.0000000000001758","DOIUrl":"https://doi.org/10.1097/CAD.0000000000001758","url":null,"abstract":"<p><p>Nonsmall cell lung cancer (NSCLC) with SMARCA4 deficiency represents a rare subset of lung tumors characterized by early metastasis, poor response to chemotherapy, and unfavorable prognosis. Established therapy strategies for SMARCA4-deficient NSCLC remain elusive. While immune checkpoint inhibitors have been proposed as a potential solution, their efficacy remains uncertain. Clinical factors such as tumor mutational burden (TMB), microsatellite instability, comutations, and programmed death-ligand 1 (PD-L1) expression may influence the treatment response of SMARCA4-deficient NSCLC. Additionally, PD-L1 expression on circulating tumor cells (CTCs) provides novel insights for monitoring, and its utility in SMARCA4-deficient NSCLC remains unexplored. The present report describes the case of a 71-year-old man diagnosed with SMARCA4-deficient NSCLC who had a history of heavy smoking and chronic cough. Imaging examination revealed metastatic lymph nodes. All serum tumor markers were elevated above the normal range. Histopathological and immunohistochemical analyses of the biopsy specimen from a primary lesion in the right upper lung demonstrated irregularly arranged tumor cells, SMARCA4 deficiency, and positive PD-L1 expression. Further next-generation sequencing confirmed SMARCA4 mutation, high TMB, and microsatellite stability (MSS). The patient received pembrolizumab treatment and experienced a sustained benefit for >40 months, with persistent PD-L1 expression on CTCs observed throughout the treatment. It was revealed that pembrolizumab therapy shows promise for patients with SMARCA4-deficient NSCLC with positive PD-L1 expression, high TMB, and MSS. Dynamic monitoring of PD-L1 status on CTCs may facilitate the assessment of the immunotherapy response, and the sustained positive PD-L1 expression on CTCs may imply continued benefit from immunotherapy for patients with SMARCA4-deficient NSCLC.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032536","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":"Anlotinib for the treatment of pulmonary epithelioid inflammatory myofibroblastic sarcoma: a case report.","authors":"Huanling Zeng, Xin Li, Shengli Chen, Jiajian Xu, Yue Xiao, Yuhua Zhao","doi":"10.1097/CAD.0000000000001731","DOIUrl":"10.1097/CAD.0000000000001731","url":null,"abstract":"<p><p>Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare subtype of inflammatory myofibrosarcoma. Anlotinib has demonstrated efficacy in the treatment of sarcoma. Nevertheless, to our knowledge, its use in EIMS has not been reported. Herein, we present a case of pulmonary EIMS. The patient underwent two courses of chemotherapy with doxorubicin combined with ifosfamide; however, the treatment was switched to anlotinib due to leukocytopenia. After 11 months of treatment with anlotinib, the tumor was in partial remission. Subsequently, the patient developed an acute myocardial infarction, which resulted in the discontinuation of anlotinib. Four months after discontinuation, the tumor progressed and anlotinib therapy was resumed. Following treatment for 5 months, tumor assessment indicated partial remission until March 2024. During this period, the patient experienced an adverse effect (i.e. ostealgia), which led to two reductions in the dosage of anlotinib. This case report provides a novel strategy for treating EIMS.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"678-681"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966467","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}

{"title":"APG-115 synergizes with bortezomib to induce apoptosis in cervical cancer cells.","authors":"Chuanyue Sun, Xueqiong Meng, Xiaoxi Cui, Shihao Liang, Jie Sun, Binghui Zhang, Yanhong Cui, Yinzhen Zhao, Ning Chen, Kangli Tian, Yixiang Chen","doi":"10.1097/CAD.0000000000001735","DOIUrl":"10.1097/CAD.0000000000001735","url":null,"abstract":"<p><p>Despite significant advancements in vaccination, screening, and therapeutic strategies have substantially reduced cervical cancer incidence, effective treatment for this disease remains a major clinical challenge. This study reveals that APG-115, a murine double minute 2 (MDM2) inhibitor, upregulates the transcription and expression of MDM2, p53, and p21, effectively inhibiting cell proliferation and inducing apoptosis in cervical cancer cells. Mechanistically, APG-115 suppresses the activation of the AKT and ERK signaling pathways and reduces the expression of antiapoptotic proteins BCL-2, BCL-xL, and MCL-1, while promoting the expression of pro-apoptotic proteins BAK, BAX, and BIM. Notably, the combination of APG-115 with bortezomib enhances p53 and p21 expression, synergistically induces cell apoptosis. In the cervical cancer xenograft models, APG-115 and bortezomib significantly downregulated the expression of Ki67 and BCL-2 while markedly increasing p21 protein levels, effectively suppressing tumor growth and inducing apoptosis. The combination further amplified the effects on Ki67, BCL-2, and p21 expression, leading to enhanced tumor growth inhibition. In summary, this study demonstrates that APG-115 exerts antitumor effects in cervical cancer, and its combination with bortezomib further enhances this inhibitory effect, probably through maximal activation of p53 and inhibition of BCL-2, suggesting a potential application of APG-115 in the treatment of cervical cancer.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"637-647"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207468","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}

{"title":"Synthesis, characterization and evaluation of linoleic acid-loaded nano-carriers: a novel drug delivery system for efficient treatment of hepatocellular carcinoma.","authors":"Mahsa Ghasemzad, Haleh Bakhshandeh, Roghayeh Naserkhaki, Ibrahim Ghoytasi, Bahare Shokoohian, Alireza Fotouhi, Zohreh Miri-Lavasani, Elham Rismani, Nikoo Hossein-Khannazer, Abbas Piryaei, Massoud Vosough","doi":"10.1097/CAD.0000000000001734","DOIUrl":"10.1097/CAD.0000000000001734","url":null,"abstract":"<p><p>Hepatocellular carcinoma is the main primary liver cancer. Due to the high recurrence rate and potential resistance to treatments, there is an urgent need to find more effective and targeted therapies. Combinational therapies and using advanced drug delivery methods are promising approaches. Niosomes are one of the popular types of nanoparticles in modern drug delivery systems and have recently attracted more attention. They are biodegradable, nonimmunogenic, and more stable carriers than liposomes. They can release anticancer drugs in an efficient and controlled manner. The aim of this study was to synthesize and characterize the physicochemical properties of linoleic acid (LA)-loaded niosomes and evaluate their anticancer effects on a hepatoma cell. We synthesized LA-loaded niosomes using a thin-film hydration method and characterized their size, polydispersity index (PDI), and zeta potential. The morphology of niosomes was evaluated by scanning electron microscopy. Finally, the viability, migration capacity, and colonization potential of Hep-3B hepatoma cells treated with 150 μM LA-loaded niosomes were investigated and compared to the control groups. The niosomes had a mean size of 266.9 nm, PDI of 0.271, and zeta potential of -26.1 mV. The LA-loaded niosomes released LA sustainably at 37 °C for 72 h. MTS assay indicated that the LA-loaded niosomes were more toxic than free LA. Hep-3B hepatoma cells treated with LA-loaded niosomes showed a remarkable decline in the migration ability and colony-formation capacity. Therefore, the use of LA-loaded niosomes in combination with conventional protocols may be a promising approach to target cancer cells.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"629-636"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172455","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":"A case of diabetic ketoacidosis triggered by immune checkpoint inhibitors in the treatment of recurrent nasopharyngeal carcinoma.","authors":"Shuting Xian, Liu Yang, Chunmiao Wang, Jinxin Cao, Danxian Jiang, Jing Huang","doi":"10.1097/CAD.0000000000001739","DOIUrl":"10.1097/CAD.0000000000001739","url":null,"abstract":"<p><p>Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) have been widely documented. Diabetic ketoacidosis (DKA), a severe irAEs, has not been previously reported in patients with nasopharyngeal carcinoma (NPC). This case report describes the development of DKA during maintenance immunotherapy with tislelizumab in a patient with recurrent NPC. A 41-year-old female patient with recurrent NPC (rT3N0M0, 8 th edition of AJCC staging) experienced DKA during her 13 th session of maintenance treatment with the ICI tislelizumab. After urgent consultation with an endocrinologist, immune-related DKA was diagnosed, and immune checkpoint inhibitor-related diabetes was confirmed. Prompt treatment with hypoglycemic agents, fluid infusion, and correction of water-electrolyte and acid-base balance was administered. The patient's blood glucose was stabilized within 6 days, and she was discharged without complications. This is the first reported case of DKA in a patient with NPC receiving tislelizumab maintenance immunotherapy. Clinicians should enhance their understanding and monitoring of adverse events in patients treated with ICIs, focusing on early diagnosis and appropriate intervention.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"694-697"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172414","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":"Novel dibenzoylmethane derivative 2-allyl-1,3-diphenyl-1, 3-propanedione: a safe and effective topical treatment for melanoma.","authors":"Jefferson Viktor de Paula Barros Baeta, Maria Aparecida Braga Rocha E Oliveira, Fernada Rodrigues Nascimento, Marcos Rodrigo de Oliveira, Virgínia Ramos Pizziolo, Tiago Antônio de Oliveira Mendes, Gaspar Diaz-Muñoz, Anésia Aparecida Dos Santos, Marisa Alves Nogueira Diaz","doi":"10.1097/CAD.0000000000001730","DOIUrl":"10.1097/CAD.0000000000001730","url":null,"abstract":"<p><p>This study investigated 2-allyl-1,3-diphenyl-1,3-propanedione (DPAP), a dibenzoylmethane derivative, as a potentially more effective and safer alternative to dacarbazine for melanoma treatment. The antitumor activity of DPAP was assessed through comprehensive in-vitro, in-silico, and in-vivo experiments. In-vitro assays evaluated DPAP's IC 50 values against melanoma cells, benchmarking its efficacy against dacarbazine. Molecular analyses explored apoptosis mechanisms, emphasizing the roles of FAS receptors and caspase pathways. In-silico absorption, distribution, metabolism, excretion, and toxicity analysis provided insights into DPAP's pharmacokinetic profile, including absorption, distribution, metabolism, and toxicity. In-vivo studies examined its effects on tumor volume, vascular endothelial growth factor (VEGF) levels, and the histopathology of the liver, kidney, and lymph nodes. DPAP demonstrated significantly enhanced antitumor activity, reflected by markedly lower IC 50 values compared with dacarbazine, underscoring its superior efficacy and specificity toward tumor cells. Molecular assays confirmed that DPAP induces apoptosis through modulation of FAS receptors and activation of caspase pathways. In-silico results revealed favorable pharmacokinetic properties, including high intestinal absorption and good tissue distribution, with no evidence of carcinogenic potential. Notably, in-vivo experiments showed that DPAP effectively reduced tumor volume and VEGF levels, while also preventing hepatotoxicity and nephrotoxicity. In addition, it inhibited the migration of tumor cells to lymph nodes. These findings position DPAP as a promising candidate for melanoma treatment, particularly as a topical therapeutic, offering enhanced efficacy and safety compared with existing treatments. DPAP is a promising candidate for melanoma treatment, particularly through topical application, offering a safer and more effective alternative to current treatments.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"607-621"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315774","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":"Benefit of switching to firmonertinib following almonertinib-induced interstitial pneumonitis in a patient with advanced non-small-cell lung cancer: a case report.","authors":"Lingying Wang, Pan Yang, Hu Luo","doi":"10.1097/CAD.0000000000001742","DOIUrl":"10.1097/CAD.0000000000001742","url":null,"abstract":"<p><p>Almonertinib, a representative epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is the first-line standard treatment for EGFR-mutant advanced non-small-cell lung cancer; however, it may induce drug-related interstitial lung disease (ILD). This case report presents a 67-year-old female with advanced lung adenocarcinoma, who was diagnosed with an EGFR exon 19 deletion mutation. After 2 months of first-line almonertinib treatment (110 mg/day), a PR was achieved; however, progressive respiratory distress emerged. Chest computed tomography revealed ground-glass opacities accompanied by grid-like changes in both lungs, leading to a diagnosis of EGFR-TKI-related ILD (grade 2). Following glucocorticoid treatment and medication discontinuation, the lung lesions improved. Given the persistent tumor activity, the patient was switched to firmonertinib (80 mg/day) for targeted therapy. This switch did not lead to a recurrence of ILD symptoms, with a progression-free survival exceeding 5 months and good tolerability. This suggests that for patients with ILD associated with almonertinib and firmonertinib may serve as an effective and safe alternative. Closely monitoring ILD in clinical practice and promptly switching to similar drugs may avoid chemotherapy intervention and optimize treatment strategies. This case marks the first report of clinical experience achieving sustained remission by switching to a similar drug, firmonertinib, in patients with ILD related to almonertinib.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"682-685"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214662","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}

{"title":"Rapid radiological response of leptomeningeal carcinosis and prolonged survival to encorafenib and binimetinib in BRAF-mutated melanoma.","authors":"Giacomo Corradi, Sara De Martino, Angela Rinaldi, Giambattista Siepe, Paola V Marchese, Barbara Melotti, Francesca Comito","doi":"10.1097/CAD.0000000000001737","DOIUrl":"10.1097/CAD.0000000000001737","url":null,"abstract":"<p><p>Among solid tumors, malignant melanoma (MM) has the highest risk of metastasis to the leptomeninges, for which a specific therapeutic regimen has not been established yet. This case report describes a rapid partial response to leptomeningeal disease (LMD) in a patient with a BRAF V600K-mutated MM. A 69-year-old man affected by metastatic melanoma was initially treated with benefit with targeted therapy with encorafenib and binimetinib, which was discontinued several times because of toxicity or intolerance, and then with dabrafenib and trametinib, which were also poorly tolerated. During the treatment pause, the patient, who had refused to receive immunotherapy developed LMD and was started again on targeted therapy with reduced dosage of encorafenib and binimetinib. A few days after starting this treatment, MRI showed an important reduction of the perilesional edema and then, after a few months, a disease response. The patient had a long survival of approximately 14 months from this diagnosis. To the best of our knowledge, this is the first report describing rapid radiological response, clinical benefit, and prolonged survival with encorafenib and binimetinib in patients affected by LMD from melanoma.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"691-693"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172452","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}