Cancers最新文献

{"title":"Can PSMA-Targeting Radiopharmaceuticals Be Useful for Detecting Brain Metastasis of Various Tumors Using Positron Emission Tomography?","authors":"Esra Arslan, Nurhan Ergül, Rahime Şahin, Ediz Beyhan, Özge Erol Fenercioğlu, Yeşim Karagöz, Arzu Algün Gedik, Yakup Bozkaya, Tevfik Fikret Çermik","doi":"10.3390/cancers17183088","DOIUrl":"10.3390/cancers17183088","url":null,"abstract":"<p><p><b>Objective:</b> The high expression of prostate-specific membrane antigen (PSMA) associated with neovascularization in non-prostatic malignant tumors and metastatic lesions has been documented in many studies. By taking advantage of the absence of PSMA-related background activity in brain tissue, in recent years, PSMA has been used for the imaging of glial tumors, especially for postoperative follow-up. The aim of this prospective study was to investigate the diagnostic value of <sup>68</sup>Ga-PSMA-11 PET/CT by comparing <sup>68</sup>Ga-PSMA-11 PET/CT, <sup>18</sup>F-FDG PET/CT, and MRI findings in patients with brain metastases (BM). <b>Materials and Method:</b> In this prospective study, 27 cases, 11 female and 16 male, with a mean age of 59.48 ± 12.21 years, were included. Patients diagnosed with BM on <sup>18</sup>F-FDG PET/CT or CT/MRI at initial diagnosis or in the follow-up period were included in the study. PET findings of BM lesions obtained from <sup>18</sup>F-FDG and <sup>68</sup>Ga-PSMA-11 PET/CT imaging, demographic characteristics, histopathological data of the primary foci, and other clinical features were evaluated together. <b>Results:</b> Twenty-four (89%) patients were included in the study for restaging, two (7%) patients for local recurrence assessment, and one (4%) patient for local recurrence and suspicion of additional lesions. The indications for <sup>18</sup>F-FDG PET/CT were breast carcinoma for 37% (n:10), followed by lung carcinoma for 26% (n:7), colorectal adenocarcinoma for 14% (n:4), squamous cell larynx carcinoma for 7% (n:2), gastric signet ring cell carcinoma for 4% (n:1), pancreatic NET3 for 4% (n:1), thyroid papillary carcinoma for 4% (n:1), and malignant melanoma for 4% (n:1). In total, 26/27 included patients had PSMA-positive brain metastases but only one patient had PSMA-negative brain metastases with <sup>68</sup>Ga-PSMA-11 PET/CT imaging. This patient was followed with a diagnosis of primary larynx squamous carcinoma and had a mass suspected of brain metastases. Further tests and an MRI revealed that the lesion in this patient was a hemorrhagic metastasis. The smallest metastatic focus on <sup>68</sup>Ga-PSMA-11 PET/CT imaging was 0.22 cm, also confirmed by MRI (range: 0.22-2.81 cm). The mean ± SD SUVmax of the BM lesions was 17.9 ± 8.6 and 6.8 ± 5.2 on <sup>18</sup>F-FDG PET/CT and <sup>68</sup>Ga-PSMA-11 PET/CT imaging, respectively. Metastatic foci that could not be detected by <sup>18</sup>F-FDG PET/CT imaging were successfully detected with <sup>68</sup>Ga-PSMA-11 PET/CT imaging in 11 cases (42%). The distribution and number of metastatic lesions observed on cranial MRI and <sup>68</sup>Ga-PSMA-11 PET/CT were compatible with each other for all patients. Immunohistochemical staining was performed in the primary tumor of 10 (38%) cases, and positive IHC staining with PSMA was detected in 5 patients. In addition, positive IHC staining with PSMA was detected in all of the four surgically excise","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast Immunology Network: Toward a Multidisciplinary and Integrated Model for Breast Cancer Care in Italy.","authors":"Andrea Botticelli, Ovidio Brignoli, Francesco Caruso, Giuseppe Curigliano, Vincenzo Di Lauro, Carla Masini, Mario Taffurelli, Giuseppe Viale","doi":"10.3390/cancers17183089","DOIUrl":"10.3390/cancers17183089","url":null,"abstract":"<p><p><b>Background:</b> Breast cancer is the most common female cancer in Italy. Despite better survival rates, significant disparities in access to diagnosis, treatment, and follow-up persist across regions. We propose an integrated, multidisciplinary care model-the Breast Immunology Network (BIN)-to address these challenges. <b>Methods:</b> The model was developed through a two-phase expert consultation with key opinion leaders and stakeholders, aligned with national and European oncology guidelines. No new patient data were collected; this is a qualitative analysis based on expert consensus and existing literature. The proposed model integrates a Hub-and-Spoke cancer network structure with fully functioning multidisciplinary teams (MDTs), standardized care pathways (PDTA), and digital tools to ensure continuity of care. <b>Results:</b> Experts identified critical gaps in Italy's breast cancer care: limited access to specialized centers, inconsistent adherence to screening programs, and delays in treatment initiation. The proposed BIN model aims to bridge these gaps by enhancing collaboration across all care levels, incorporating immunotherapy where appropriate, and defining key performance indicators (KPIs) for continuous quality evaluation. For example, quantitative targets include achieving ≥65% nationwide mammography screening adherence and ensuring ≥90% of patients are treated in certified Breast Units. <b>Conclusions:</b> The Breast Immunology Network offers a strategic framework to improve equity, quality, and timeliness of breast cancer care in Italy. Importantly, unlike existing Hub-Spoke or CCCN models, the BIN formalizes governance tools, harmonized eligibility criteria, and a national registry for immunotherapy. By uniting Breast Units and community services under shared governance, and by integrating innovations such as immunotherapy and telemedicine, the BIN model could significantly improve clinical outcomes and ensure more equitable care for all patients. Its implementation may serve as a reference model for other health systems seeking to optimize oncology pathways through multidisciplinary integration and advanced treatments.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12469181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma: Aligning Guideline Recommendations with Real-World Evidence.","authors":"Roberto Cammarata, Alberto Catamerò, Vincenzo La Vaccara, Roberto Coppola, Damiano Caputo","doi":"10.3390/cancers17183085","DOIUrl":"10.3390/cancers17183085","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a 5-year overall survival below 12% and high recurrence rates even after R0 resection. Traditionally managed with a \"surgery-first\" approach, two consistent observations-the near-universal presence of micrometastatic disease at diagnosis and the frequent inability to complete adjuvant therapy-have driven the integration of neoadjuvant therapy (NAT) into clinical practice. NAT offers several theoretical and practical advantages: early systemic control of occult disease, improved delivery and completion of multimodal treatment, biological selection of surgical candidates, and increased R0 resection rates. While in borderline resectable PDAC, randomized trials have consistently demonstrated improved margin-negative resection rates and early survival benefits compared with upfront surgery, in resectable PDAC, evidence is more heterogeneous. Real-world studies corroborate trial findings, reporting higher R0 rates and reduced lymph node positivity without increased perioperative risk, but also highlight substantial heterogeneity in regimens, duration, and radiotherapy use. Limitations to universal NAT adoption include reliance on anatomy-based resectability criteria, absence of validated predictive biomarkers, challenges in response assessment, and concerns over disease progression during preoperative treatment. Future developments will focus on integrating molecular profiling, circulating tumor DNA dynamics, and advanced imaging into patient selection and treatment adaptation, supported by biomarker-enriched and adaptive trial designs. NAT is thus evolving from a selective strategy for borderline disease to an innovative framework to optimize multimodal treatment delivery and refine patient selection in PDAC, with the potential to improve surgical outcomes and inform systemic therapy decisions in both resectable and borderline resectable settings.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laser Indirect Ophthalmoscopy-Guided Transpupillary Thermotherapy Versus I-125 Plaque Brachytherapy for Choroidal Hemangioma.","authors":"Rima Torosyan, Imad Jaradat, Reem AlJabari, Mona Mohammad, Ibrahim AlNawaiseh, Yacoub A Yousef","doi":"10.3390/cancers17183087","DOIUrl":"10.3390/cancers17183087","url":null,"abstract":"<p><p><b>Background:</b> Choroidal hemangioma, a rare benign vascular tumor, can cause visual loss due to subretinal fluid. Photodynamic therapy (PDT) with verteporfin has been the standard treatment, with plaque brachytherapy reserved for PDT failure. Verteporfin is unavailable in many regions in the Middle East, including Jordan, leaving plaque as the main alternative; however, plaque often leads to poor visual outcomes despite tumor control. To improve visual outcomes, we introduced transpupillary thermotherapy (TTT) via laser indirect ophthalmoscopy (LIO) as a practical, widely available, vision-preserving treatment. <b>Methods:</b> We retrospectively reviewed 13 patients with choroidal hemangioma treated at King Hussein Cancer Center. Patients received either plaque brachytherapy or LIO-guided TTT. Clinical data included visual acuity at baseline, tumor thickness reduction, subretinal fluid status, and visual outcome. <b>Results:</b> All patients had unilateral circumscribed choroidal hemangioma, and 10 (77%) were males. At diagnosis, the visual acuity was ≤0.5 in all patients (100%) and <0.1 in six (46%) patients. Seven patients (54%) received LIO-guided TTT and six (46%) underwent I-125 plaque brachytherapy. Tumor thickness was 3.0-5.0 mm in 12 (92%) cases; the median thickness in the I-125 plaque brachytherapy group was 4.5 mm (range, 4.5-5.0 mm), whereas in the LIO-guided TTT group it was 3.8 mm (range, 2.9-5.0 mm). At a median follow-up of 20 months (mean 24, range 12-48 months), five out of seven patients (71%) treated with TTT showed significant visual improvement, while the remaining two (29%) had stable vision; none experienced deterioration. In contrast, none of the six plaque-treated patients (0%) demonstrated any improvement in visual acuity; four remained stable and two worsened. This difference was statistically significant (<i>p</i> = 0.021). Tumor thickness was reduced in both groups, with a median reduction of -56% in the plaque group and -36% in the TTT group. All patients achieved complete resolution of subretinal fluid. <b>Conclusions:</b> LIO-guided TTT is an effective vision-preserving treatment for choroidal hemangioma. While both modalities-controlled tumor growth, only TTT resulted in significant visual improvement. This study demonstrates that LIO-guided TTT can replace plaque brachytherapy in regions where verteporfin (PDT) is unavailable, offering an accessible, practical, and superior alternative for preserving vision in patients with choroidal hemangioma.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRG1 Loss Is Frequent in Lung Cancer and Transforms Lung Epithelial Cells via Transcriptional and Epigenetic Reprograming.","authors":"Mathewos Tessema, Christin M Yingling, Loryn M Phillips, Kieu Do, Maria A Picchi, Randy Willink, Steven A Belinsky","doi":"10.3390/cancers17183092","DOIUrl":"10.3390/cancers17183092","url":null,"abstract":"<p><strong>Background/objectives: </strong>The BRG1 loss-of-function (LOF) mutation is found in ~10% of non-small cell lung cancer (NSCLC) cases, but its role in lung tumorigenesis is unclear and so it is investigated in this study.</p><p><strong>Methods: </strong>BRG1-knockout (KO) lines were generated from various non-malignant, pre-malignant, and malignant human lung epithelium-derived cell lines using CRISPR. The effects of BRG1-KO on cell growth, the transcriptome, the methylome, and epigenetic therapy were compared with those of wild-type (BRG1-WT) isogenic controls using standard in vitro and in vivo assays.</p><p><strong>Results: </strong>The BRG1 protein was expressed in all non-/pre-malignant lung epithelial cells but lost in 47% (14/30) of NSCLC cell lines. BRG1-KO and cigarette smoke (CS) exposure individually transformed human bronchial epithelial cell lines (HBECs), as evidenced by anchorage-independent growth. BRG1-KO and CS produced additive to synergistic effects on sensitivity to transformation that differed across HBECs. RNA-seq analysis revealed that BRG1-KO significantly changed the expression of over 8500 genes on average, impacting lung development, function, damage repair, and cancer pathways, including axonal guidance, pulmonary wound healing, and epithelial-to-mesenchymal transition (EMT). BRG1-KO also led to the hypermethylation of >47,000 promoter CpGs within ~9500 genes on average in different HBECs, including silencing of epithelial genes involved in EMT and tumor suppressor genes. BRG1-KO also moderately increased the in vitro and in vivo sensitivity of NSCLC cells to some epigenetic drugs.</p><p><strong>Conclusions: </strong>BRG1-LOF is frequent in NSCLC; can drive the transformation of lung epithelial cells such that they acquire properties of pre-malignant cells, indicating a potential role in lung cancer initiation; and sensitizes lung tumors to epigenetic therapy.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgical Strategies for Tumors of the Pancreas and Duodenum.","authors":"Rosyli F Reveron-Thornton, Kelly X Huang, Daniel Delitto, Michael T Longaker, Jeffrey A Norton","doi":"10.3390/cancers17183091","DOIUrl":"10.3390/cancers17183091","url":null,"abstract":"<p><p>The recommended surgery for pancreatic tumors is dependent on the diagnosis. For pancreatic adenocarcinoma, duodenal, and ampullary adenocarcinoma, a Whipple pancreaticoduodenectomy with lymph node dissection is recommended. For small < 2 cm or non-imageable gastrinomas, duodenal transillumination, duodenotomy, duodenal tumor excision and adjacent lymphadenectomy is recommended. For large > 3 cm gastrinomas, a Whipple pancreaticoduodenectomy with adjacent lymph node dissection is recommended. For small 1-2 cm insulinomas, intraoperative ultrasound with enucleation is recommended. If the patient with gastrinoma, insulinoma, or multiple nonfunctional NETs occurs in the setting of MEN-1, a subtotal pancreatectomy with or without splenectomy with enucleation of pancreatic head tumors is recommended, with adjacent lymph node dissection. The detail of each procedure is described with illustrations.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contrast-Enhanced Mammography-Guided Biopsy in Patients with Extensive Suspicious Microcalcifications.","authors":"Yun-Chung Cheung, Wai-Shan Chung, Ya-Chun Tang, Chia-Wei Li","doi":"10.3390/cancers17183086","DOIUrl":"10.3390/cancers17183086","url":null,"abstract":"<p><p><b>Objectives</b>: To investigate the feasibility of contrast-enhanced mammography-guided biopsy (CEM-Bx) to diagnose cancer via targeting the associated enhancements in the patients with extensive suspicious microcalcifications. <b>Methods</b>: All the women with extensive suspicious microcalcifications were mammographically screened. Contrast-enhanced mammography was first examined, followed by CEM-Bx if there was any relevant enhancement; otherwise, patients without enhancement were submitted to conventional mammography-guided biopsy (MG-Bx). We recorded and analyzed the histological results, morphologies and distributions of the microcalcifications. The outcomes were also compared to those patients (control group) who did not assess with CEM and received MG-Bx only by the Wilcoxon rank-sum test. <b>Results</b>: Between November 2021 and November 2023, a total of 61 participants participated in the test. A total of 26 women underwent CEM-Bx, and 35 underwent MG-Bx. In total, 19 of the 26 CEM-Bx were diagnosed as cancer, and none by MG-Bx. The cancer diagnostic rates (CDRs) identified by CEM-Bx were 81.8% for regional microcalcifications and 66.7% for segmental or diffuse distributions. The CDR of the test group was higher than the control group, 31.4% to 20%, respectively. Otherwise, the CDR of CEM-Bx was significantly higher than MG-Bx in the control group (73.08% to 20%, <i>p</i>-valve < 0.01). <b>Conclusions</b>: CEM-Bx was a safe and feasible procedure. With identification of the enhanced target, CEM-Bx faithfully performed among the extensive distributed suspicious microcalcifications. Although CEM-Bx improves CDR, larger prospective trials with surgical validation of all lesions are needed before widespread adoption.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies to Target the Tumor-Associated Macrophages in the Immunosuppressive Microenvironment of Pancreatic Ductal Adenocarcinoma.","authors":"Ryu Matsumoto, Kiyonori Tanoue, Chieri Nakayama, Masashi Okawa, Yuto Hozaka, Tetsuya Idichi, Yuko Mataki, Takao Ohtsuka","doi":"10.3390/cancers17183090","DOIUrl":"10.3390/cancers17183090","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is a critical disease requiring the development of novel effective therapeutic approaches due to its increasing global incidence and associated low survival rates. While immunotherapy, including immune checkpoint inhibitors, has shown efficacy against various tumors, developing an effective treatment approach for PDAC poses a challenge. This is primarily attributed to the complex and distinctive immune evasion mechanisms of PDAC. Recent studies have revealed that tumor-associated macrophages (TAMs) play a crucial role in enhancing immune evasion in PDAC. This role is mediated through multiple pathways, including cytokine secretion and the activation or suppression of diverse immune cells. A clear understanding of how macrophages contribute to PDAC proliferation could lead to the development of novel immune therapy approaches targeting TAMs. In this review, we summarized the multifaceted activities and roles of TAMs in PDAC and explored the potential effect of immunotherapeutic approaches on PDAC, with a particular focus on chimeric antigen receptor (CAR) macrophages. This review was based on promising findings from recent studies on CAR macrophage-based immunotherapy for solid tumors.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiopathological Features in a Three-Dimensional In Vitro Model of Hepatocellular Carcinoma: Hypoxia-Driven Oxidative Stress and ECM Remodeling.","authors":"Maria Giovanna Rizzo, Enza Fazio, Claudia De Pasquale, Emanuele Luigi Sciuto, Giorgia Cannatà, Cristiana Roberta Multisanti, Federica Impellitteri, Federica Gilda D'Agostino, Salvatore Pietro Paolo Guglielmino, Caterina Faggio, Sabrina Conoci","doi":"10.3390/cancers17183082","DOIUrl":"10.3390/cancers17183082","url":null,"abstract":"<p><p><i>Background</i>: Hypoxia is a hallmark of solid tumors, including hepatocellular carcinoma (HCC), where it drives oxidative stress and extracellular matrix (ECM) remodeling, promoting tumor invasion and metastasis. Investigating these mechanisms in patients remains challenging due to the complexity of the tumor microenvironment. <i>Methods</i>: We developed a scaffold-free three-dimensional (3D) spheroid model of HCC using human hepatocellular carcinoma HepG2 cells (ATCC HB-8065). To characterize hypoxia-driven processes, a multiparametric approach combining MTT assays for metabolic activity, confocal microscopy for viability and ECM organization, flow cytometry for apoptosis and ROS detection, qRT-PCR for gene expression, and FTIR spectroscopy for biochemical profiling were performed. <i>Results</i>: The 3D model exhibited progressive ROS accumulation, stabilization of HIF-1α, and metabolic reprogramming toward aerobic glycolysis. In parallel, ECM remodeling was evident, with increased expression of SPARC and FN1 and collagen fiber alignment, reflecting an invasive tumor phenotype. <i>Conclusions</i>: This scaffold-free 3D HCC model recapitulates key physiopathological features of tumor progression, providing a robust and physiologically relevant platform to investigate the hypoxia-ROS-ECM relationship and to support preclinical evaluation of targeted therapeutic strategies.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real World Data on the Efficacy of Brigatinib in ALK-Positive Non-Small Cell Lung Cancer: A Single-Center Experience.","authors":"Vesna Ćeriman Krstić, Natalija Samardžić, Mihailo Stjepanović, Spasoje Popević, Tatjana Adžić-Vukičević, Sofija Glumac, Ruža Stević, Dragana Marić, Marta Velinović, Milena Jovanović, Branislav Ilić, Milija Gajić, Nikola Čolić, Katarina Lukić, Brankica Milošević Maračić, Slavko Stamenić, Ivana Sekulović Radovanović, Jelena Milin Lazović","doi":"10.3390/cancers17183084","DOIUrl":"10.3390/cancers17183084","url":null,"abstract":"<p><p><b>Introduction</b>: Lung cancer remains the leading cause of cancer death among all cancers. The discovery of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations led to an increased survival rate in patients with locally advanced and metastatic non-small cell lung cancer (NSCLC). Results of the ALTA 1L study showed superior outcomes for patients treated with brigatinib compared to patients treated with crizotinib. <b>Background</b>: We conducted research including 23 patients with ALK-positive lung adenocarcinoma who were treated with brigatinib in first or further lines of therapy. The median follow-up was 22 months (4-66 months). <b>Results</b>: There were no significant differences in patient population between the first and further lines of treatment regarding sex distribution (<i>p</i> = 0.692), smoking status (<i>p</i> = 0.554), ECOG performance status (<i>p</i> = 1.000), and baseline presence of brain metastases (<i>p</i> = 0.862). The response rate was 47.8%, and disease control was 95.6%. The 12-month progression-free survival (PFS) and overall survival (OS) rates were 85.3% and 86.5%, respectively, while the 60-month PFS rate was not reached, and the 60-month OS rate was 27.1%. The mPFS and mOS were 32 months. <b>Conclusions:</b> The results of this analysis are promising, as our patients experienced better outcomes compared to those in the ALTA 1L study, which may be attributed to the small sample size. However, the effectiveness of brigatinib has been confirmed in our clinical practice.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}