Current oncology最新文献

{"title":"The Role of the DNA Methyltransferase Family and the Therapeutic Potential of DNMT Inhibitors in Tumor Treatment.","authors":"Dae Joong Kim","doi":"10.3390/curroncol32020088","DOIUrl":"10.3390/curroncol32020088","url":null,"abstract":"<p><p>Members of the DNA methyltransferase (DNMT) family have been recognized as major epigenetic regulators of altered gene expression during tumor development. They establish and maintain DNA methylation of the CpG island of promoter and non-CpG region of the genome. The abnormal methylation status of tumor suppressor genes (TSGs) has been associated with tumorigenesis, leading to genomic instability, improper gene silence, and immune evasion. DNMT1 helps preserve methylation patterns during DNA replication, whereas the DNMT3 family is responsible for de novo methylation, creating new methylation patterns. Altered DNA methylation significantly supports tumor growth by changing gene expression patterns. FDA-approved DNMT inhibitors reverse hypermethylation-induced gene repression and improve therapeutic outcomes for cancer. Recent studies indicate that combining DNMT inhibitors with chemotherapies and immunotherapies can have synergistic effects, especially in aggressive metastatic tumors. Improving the treatment schedules, increasing isoform specificity, reducing toxicity, and utilizing genome-wide analyses of CRISPR-based editing to create personalized epigenetic therapies tailored to individual patient needs are promising strategies for enhancing therapeutic outcomes. This review discusses the interaction between DNMT regulators and DNMT1, its binding partners, the connection between DNA methylation and tumors, how these processes contribute to tumor development, and DNMT inhibitors' advancements and pharmacological properties.</p>","PeriodicalId":11012,"journal":{"name":"Current oncology","volume":"32 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491250","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":"The Efficacy and Safety of Hepatic Artery Infusion Chemotherapy Combined with Lenvatinib and Programmed Death (PD)-1 Inhibitors for Unresectable Intrahepatic Cholangiocarcinoma: A Retrospective Study.","authors":"Yingxiao Cai, Wu Wen, Yangshuo Xia, Renhua Wan","doi":"10.3390/curroncol32020087","DOIUrl":"10.3390/curroncol32020087","url":null,"abstract":"<p><p><b>Objectives:</b> Although systemic chemotherapy (SC) is the mainstay for treating unresectable intrahepatic cholangiocarcinoma (ICC), its efficacy is limited and it causes severe systemic side effects. This study focuses on evaluating the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib plus programmed death-1 (PD-1) inhibitors (HLP), compared to SC in combination with lenvatinib plus PD-1 inhibitors (SCLP) for unresectable ICC. <b>Methods:</b> We analyzed patients initially diagnosed with unresectable ICC at our center between March 2021 and December 2023, classifying them into HLP and SCLP groups according to treatment regimen. This study assessed and compared overall survival (OS), progression-free survival (PFS), tumor response, and safety outcomes across the two treatment groups. <b>Results:</b> This study enrolled 53 subjects in total; 25 were treated with HLP and 28 with SCLP. The two groups showed well-matched baseline characteristics. The HLP group reported an extended median OS (12.8 vs. 11.0 months, <i>p</i> = 0.310) and a prolonged median PFS (8.8 vs. 6.4 months, <i>p</i> = 0.043), compared to the SCLP group. The HLP group had a better objective response rate (ORR) (52% vs. 25%, <i>p</i> = 0.043) and disease control rate (DCR) (96% vs. 78.6%, <i>p</i> = 0.104). Based on OS (<i>p</i> = 0.019) and PFS (<i>p</i> = 0.032) results, those without extrahepatic metastasis seemed to benefit more significantly from the HLP regimen than from the SCLP regimen. The HLP group experienced fewer grade 3-4 adverse events (AEs) than the SCLP group. <b>Conclusions:</b> The HLP regimen for unresectable ICC is an effective and safe strategy and is potentially better suited for patients without extrahepatic metastases.</p>","PeriodicalId":11012,"journal":{"name":"Current oncology","volume":"32 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491231","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":"Treatment Patterns of Pancreatic Neuroendocrine Tumor (pNET) Patients at Two Canadian Cancer Centres.","authors":"Gautham Nair, Morgan Black, Kathie Baer, Stephen Welch, David T Laidley, Rachel Goodwin, Macyn Leung, William J Phillips, Michael Vickers, Tim Asmis, Horia Marginean, Elena Tsvetkova","doi":"10.3390/curroncol32020086","DOIUrl":"10.3390/curroncol32020086","url":null,"abstract":"<p><p>Pancreatic neuroendocrine tumors (pNETs) are rare but increasingly prevalent malignancies with varied prognoses and a diverse range of treatment options, including surgery, somatostatin analogues (SSAs), chemotherapy, targeted therapy, and peptide receptor radionuclide therapy (PRRT). This retrospective cohort study analyzed treatment patterns among 189 pNET patients treated between January 2010 and June 2021 at two Canadian cancer centres: the Verspeeten Family Cancer Centre (VFCC), which offers PRRT, and the Ottawa Hospital Cancer Centre (TOHCC), which does not at the time of the study. Data on demographics, tumor characteristics, and treatment modalities were collected, and statistical analyses were conducted using chi-square, Fisher's exact test, and the Kruskal-Wallis test. Among eligible patients, 53% presented with stage IV disease. Surgical resection was the most common treatment, followed by SSAs, chemotherapy, PRRT, and targeted therapy. Stage IV patients at VFCC were significantly more likely to receive PRRT (60%) compared to TOHCC (6%) and underwent more PRRT cycles, with a higher prevalence of well-differentiated tumors observed at VFCC. With these differences it was clear that the non-PRRT centre was unable to provide patients with the same level of PRRT access during the study period compared to patients seen at the PRRT site. The findings underscore the critical role of PRRT availability in influencing treatment patterns and highlight the need for equitable access to specialized therapies across Canada to optimize outcomes for pNET patients.</p>","PeriodicalId":11012,"journal":{"name":"Current oncology","volume":"32 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491271","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":"Concurrent Neoadjuvant Chemotherapy and Radiation in Locally Advanced Breast Cancer: Impact on Locoregional Recurrence Rates.","authors":"Natalie Grindrod, Matthew Cecchini, Muriel Brackstone","doi":"10.3390/curroncol32020085","DOIUrl":"10.3390/curroncol32020085","url":null,"abstract":"<p><p>Neoadjuvant chemoradiation therapy (NCRT) is an underutilized treatment in breast cancer but may improve outcomes by impacting the tumor immune microenvironment. The aim of this study was to evaluate NCRT's impact on recurrence and the role of tumor-infiltrating lymphocytes (TILs) in treatment response. We hypothesized that NCRT reduces recurrence by upregulating TILs. Patients with locally advanced breast cancer (LABC) were treated with NCRT. Stage IIB to III patients with any molecular subtypes were eligible. The patients were matched for age, stage, and molecular subtype by a propensity score to a concurrent cohort receiving standard neoadjuvant chemotherapy (NCT) followed by adjuvant radiation. The objective of this study was to assess the patients in terms of the pathological complete response (pCR), TIL counts prior to and following treatment, and locoregional recurrence. The median follow-up was 7.2 years. Thirty NCRT patients were successfully matched 1:3 to ninety NCT patients. The NCRT cohort had no regional and locoregional recurrences (<i>p</i> = 0.036, (hazard ratio) HR [0.25], 95% confidence interval (CI) [0.06-0.94] and <i>p</i> = 0.013, HR [0.25], 95% CI [0.08-0.76], respectively), compared to 17.8% of the NCT cohort. The NCRT group had significantly more pCRs, and TILs were increased in the post-treatment pCR specimens. NCRT can improve outcomes in LABC patients, with a higher pCR and significantly lower locoregional recurrence/higher recurrence-free survival. Further trials are needed to evaluate the role of NCRT in all breast cancer patients.</p>","PeriodicalId":11012,"journal":{"name":"Current oncology","volume":"32 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491216","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":"A Dramatic Clinical Response to Trastuzumab-Deruxtecan in a Patient with HER-2 Low Breast Cancer with Untreated Leptomeningeal Metastasis and Hydrocephalus.","authors":"Sarah Hussain, Robert Nordal, Danny Ng, Morgan Willson, Xiaolan Feng","doi":"10.3390/curroncol32020081","DOIUrl":"10.3390/curroncol32020081","url":null,"abstract":"<p><p>Leptomeningeal metastasis (LM) is a rare and challenging manifestation of advanced breast cancer (ABC) with severe morbidity and mortality. Patients with LM may be asymptomatic, or present with non-specific neurologic deficits, thereby possibly delaying diagnosis. Treatment typically requires a multimodal approach for effective management, symptom relief, and quality-of-life improvement. Trastuzumab-deruxtecan (T-DXd), a humanized monoclonal antibody drug conjugate, demonstrated efficacy across diverse breast cancer subtypes expressing variable levels of HER2 proteins. Currently, T-DXd is the standard of care for patients with advanced, pretreated, HER2 low breast cancer. There is limited evidence of the response of brain metastases (BM) and leptomeningeal metastases (LM) to T-DXd in HER2-low patients, with most data extrapolated from HER2-positive breast cancer studies. This case report presents the first documented instance of a patient with debilitating, symptomatic, untreated LM and hydrocephalus demonstrating a rapid and dramatic clinical response to T-DXd. This finding holds crucial clinical relevance, highlighting the potential benefit of initiating effective systemic therapy for LM early in treatment to address both central nervous system (CNS) and non-CNS disease burden, rather than delaying systemic therapy until after radiation therapy.</p>","PeriodicalId":11012,"journal":{"name":"Current oncology","volume":"32 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491084","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":"Advancements in Locoregional Therapies for Unresectable Intrahepatic Cholangiocarcinoma.","authors":"Conor D J O'Donnell, Umair Majeed, Michael S Rutenberg, Kristopher P Croome, Katherine E Poruk, Beau Toskich, Zhaohui Jin","doi":"10.3390/curroncol32020082","DOIUrl":"10.3390/curroncol32020082","url":null,"abstract":"<p><p>Intrahepatic cholangiocarcinoma is an aggressive malignancy with rising incidence and poor outcomes. This review examines recent advancements in locoregional therapies for unresectable intrahepatic cholangiocarcinoma, focusing on external beam radiotherapy, transarterial radioembolization (TARE), hepatic artery infusion pump (HAIP) chemotherapy, and liver transplantation. Stereotactic body radiation therapy and proton beam therapy have shown promise in achieving local control and improving survival. TARE, with personalized dosimetry, has demonstrated encouraging results in select patient populations. HAIP chemotherapy, primarily studied using floxuridine, has yielded impressive survival outcomes in phase II trials. Liver transplantation, once contraindicated, is now being reconsidered for carefully selected patients with localized disease. While these locoregional approaches show potential, randomized controlled trials comparing them to standard systemic therapy are lacking. Patient selection remains crucial, with factors such as liver function, tumor burden, and molecular profile influencing treatment decisions. Ongoing research aims to optimize treatment sequencing, explore combination strategies with systemic therapies, and refine phenotype identification and patient selection criteria. As the landscape of intrahepatic cholangiocarcinoma management evolves, a multidisciplinary approach is essential to tailor treatment strategies and improve outcomes for patients with this challenging disease.</p>","PeriodicalId":11012,"journal":{"name":"Current oncology","volume":"32 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491106","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":"Evaluating the Role of Robotic Surgery Gastric Cancer Treatment: A Comprehensive Review by the Robotic Global Surgical Society (TROGSS) and European Federation International Society for Digestive Surgery (EFISDS) Joint Working Group.","authors":"Luigi Marano, Tomasz Cwalinski, Sergii Girnyi, Jaroslaw Skokowski, Aman Goyal, Silvia Malerba, Francesco Paolo Prete, Piotr Mocarski, Magdalena Kamila Kania, Maciej Świerblewski, Marek Strzemski, Luis Osvaldo Suárez-Carreón, Johnn Henry Herrera Kok, Karol Polom, Witold Kycler, Valentin Calu, Pasquale Talento, Antonio Brillantino, Francesco Antonio Ciarleglio, Luigi Brusciano, Nicola Cillara, Ruslan Duka, Beniamino Pascotto, Juan Santiago Azagra, Natale Calomino, Mario Testini, Adel Abou-Mrad, Rodolfo J Oviedo, Yogesh Vashist","doi":"10.3390/curroncol32020083","DOIUrl":"10.3390/curroncol32020083","url":null,"abstract":"<p><strong>Introduction: </strong>Robot-assisted minimally invasive gastrectomy (RAMIG) represents a significant advancement in the surgical management of gastric cancer, offering superior dexterity, enhanced visualization, and improved ergonomics compared to laparoscopic gastrectomy (LG). This review systematically evaluates the current evidence on perioperative outcomes, oncological efficacy, learning curves, and economic considerations, providing insights into RAMIG's potential role in modern gastric cancer surgery.</p><p><strong>Methods: </strong>A thorough analysis of retrospective, prospective, and meta-analytic studies was conducted to compare RAMIG with LG. Key outcomes, including operative time, intraoperative blood loss, lymph node retrieval, postoperative complications, learning curve duration, and cost-effectiveness, were assessed. Emphasis was placed on both short-term and long-term oncological outcomes to determine the clinical value of RAMIG.</p><p><strong>Results: </strong>Evidence indicates that RAMIG is associated with reduced intraoperative blood loss, lower morbidity rates, and a shorter learning curve, with proficiency achieved after 11-25 cases compared to 40-60 cases for LG. The robotic platform's articulated instruments and enhanced three-dimensional visualization enable more precise lymphadenectomy, particularly in complex anatomical regions. Despite these advantages, operative time remains longer, and costs remain higher due to system acquisition, maintenance, and consumable expenses. However, emerging data suggest a gradual narrowing of cost disparities. While short-term outcomes are favorable, further high-quality, multicenter studies are needed to validate long-term oncological efficacy and survival outcomes.</p><p><strong>Conclusion: </strong>RAMIG offers significant technical and clinical advantages over conventional LG, particularly in terms of precision and learning efficiency. However, the long-term oncological benefits and economic feasibility require further validation. Future research should focus on cost optimization, advanced technological integration such as near-infrared fluorescence and artificial intelligence, and multicenter trials to solidify RAMIG's role as a standard approach for gastric cancer surgery.</p>","PeriodicalId":11012,"journal":{"name":"Current oncology","volume":"32 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491223","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":"The Healthcare Professionals' and Patient Advocates' Perspectives on the Care for Children with Cancer in Europe-A Report from the ESCALIER Project.","authors":"Maria Otth, Marko Ocokoljic, Theodora Armenkova, Irina Ban, Samira Essiaf, Maximilian Hopfgartner, Lejla Kameric, Pamela R Kearns, Georgia Kokkinou, Carmelo Rizzari, Carina Schneider, Katrin Scheinemann","doi":"10.3390/curroncol32020084","DOIUrl":"10.3390/curroncol32020084","url":null,"abstract":"<p><p>Cancer in children and adolescents is rare. Therefore, experienced multidisciplinary teams of health care professionals and input from patient advocates are needed. Within the ESCALIER project, we present the current situation of care for children and adolescents with cancer in Europe from the perspective of these stakeholders and highlight the topics relevant for them. A survey developed by representatives from the European Society for Paediatric Oncology (SIOPE) and Childhood Cancer International-Europe (CCI-E) was sent to European paediatric oncologists and patient organizations. We analysed all six questions related to general aspects of care and ten questions especially relevant for SIOPE or CCI-E using descriptive statistics. In total, 159 paediatric oncologists from 35 European countries and 41 CCI-E member organizations from 30 countries replied. Six of the ten questions selected by SIOPE and CCI-E representatives were identical and covered topics from diagnosis to end of treatment and follow-up care. This highlights the alignment of topics relevant for both stakeholders. However, the answers provided by SIOPE and CCI-E respondents to the same questions differed to varying degrees, and answers also differed between respondents from the same country. The differences in the answers provided to our survey highlight the need to raise awareness, improve knowledge, and strengthen communication between different stakeholders, organisations, patients, and families. The stakeholders' different experiences and knowledge must be considered, and can thus strengthen common goals to provide the best possible care to children and adolescents with cancer in Europe.</p>","PeriodicalId":11012,"journal":{"name":"Current oncology","volume":"32 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491234","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":"Molecular Tumor Board-Guided Targeted Treatments for Biliary Tract Cancers in a Publicly Funded Healthcare System.","authors":"Felix E G Beaudry, Zhihao Li, Ayelet Borgida, Anudari Zorigtbaatar, Xin Wang, Maggie Hildebrand, Oumaima Hamza, Gun Ho Jang, Roxana Bucur, Anna Dodd, Julie Wilson, Rebecca C Auer, Samuel Saibil, Erica S Tsang, Arndt Vogel, Grainne M O'Kane, Steven Gallinger, Jennifer J Knox, Faiyaz Notta, Gonzalo Sapisochin, Robert C Grant","doi":"10.3390/curroncol32020080","DOIUrl":"10.3390/curroncol32020080","url":null,"abstract":"<p><p>Comprehensive molecular profiling can identify alterations in biliary tract cancer (BTC) potentially treatable with targeted therapies. However, the impact of whole-genome and transcriptome sequencing (WGTS) on therapeutic decision-making in a public healthcare system is unknown. Here, BTC patients prospectively received WGTS to inform clinical care at a large Canadian academic cancer center. We characterized the proportion of targetable alterations, the treatment recommendations generated by a molecular tumor board, targeted therapies received, patient outcomes, and the financing of these treatments. A total of 55 patients with BTC prospectively underwent WGTS to inform clinical care. Of those 55, 28 (51%, 95% CI 38-64%) harbored targetable alterations. Molecular tumor boards recommended consideration of targeted therapies for 43 (78% CI: 66-87%) of 55 cases. Among the 15 patients who progressed to second-line therapy and harbored targetable alterations, 8 received nine targeted therapies. No targeted therapies were funded through the public system, and most therapies were funded through compassionate access programs from companies. These results highlight the challenges and potential for inequities when implementing precision oncology in a publicly funded healthcare system.</p>","PeriodicalId":11012,"journal":{"name":"Current oncology","volume":"32 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491080","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":"Tumor-Associated Extracellular Matrix Obstacles for CAR-T Cell Therapy: Approaches to Overcoming.","authors":"Ilya Klabukov, Alexander E Kabakov, Anna Yakimova, Denis Baranovskii, Dmitry Sosin, Dmitry Atiakshin, Michael Ignatyuk, Elena Yatsenko, Victoria Rybachuk, Ekaterina Evstratova, Daria Eygel, Dmitry Kudlay, Vasiliy Stepanenko, Peter Shegay, Andrey D Kaprin","doi":"10.3390/curroncol32020079","DOIUrl":"10.3390/curroncol32020079","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-T cell therapy yields good results in the treatment of various hematologic malignancies. However, the efficacy of CAR-T cell therapy against solid tumors has proven to be limited, primarily because the tumor-associated extracellular matrix (ECM) creates an intractable barrier for the cytotoxic CAR-T cells that are supposed to kill cancer cells. This review unravels the multifaceted role of the tumor-associated ECM in impeding CAR-T cell infiltration, survival, and functions within solid tumors. We analyze the situations when intratumoral ECM limits the efficacy of CAR-T cell therapy by being a purely physical barrier that complicates lymphocyte penetration/migration and also acts as an immunosuppressive factor that impairs the antitumor activities of CAR-T cells. In addition, we highlight promising approaches such as engineering CAR-T cells with improved capabilities to penetrate and migrate into/through the intratumoral ECM, combination therapies aimed at attenuating the high density and immunosuppressive potential of the intratumoral ECM, and others that enable overcoming ECM-related obstacles. A detailed overview of the data of relevant studies not only helps to better understand the interactions between CAR-T cells and the intratumoral ECM but also outlines potential ways to more effectively use CAR-T cell therapy against solid tumors.</p>","PeriodicalId":11012,"journal":{"name":"Current oncology","volume":"32 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491307","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}