Medical Oncology最新文献

{"title":"Graphene quantum dot-integrated nanocomposites: a promising avenue for glioblastoma treatment.","authors":"Diksha S Unidirwade, Swati N Lade, Milind J Umekar, Sushil S Burle","doi":"10.1007/s12032-025-02967-z","DOIUrl":"10.1007/s12032-025-02967-z","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) remains one of the most aggressive and resistant to treatment types of brain cancer; hence, new therapeutic approaches are required. Recent advances in nanomedicine have positioned graphene quantum dots (GQDs) as promising candidates for targeted cancer therapy due to their exceptional physicochemical properties, biocompatibility, and multifunctional capabilities. This review examines how GQDs can be included in multifunctional nanocomposites and how they might be used to diagnose and treat GBM. We discuss the unique structural and optical characteristics of GQDs that facilitate blood-brain barrier penetration, targeted drug delivery, bioimaging, and photothermal/photodynamic therapy. The design techniques of GQD-based nanocomposites are emphasized, along with their stimulus-responsive behavior, drug-loading efficiency, and surface functionalization. The cytotoxic effects on glioblastoma cell lines, biodistribution, and biosafety profiles are also rigorously assessed, along with in vitro and in vivo research. There is also discussion of toxicity issues, scalable synthesis, and limited clinical translation. This review highlights the transformative potential of GQD-integrated nanocomposites as a next-generation therapeutic platform for effectively managing GBM.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 9","pages":"417"},"PeriodicalIF":3.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804425","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":"Induction of ER stress-mediated apoptosis in breast cancer cell line by the powerful alkylating agent bendamustine and insights into its molecular mechanisms.","authors":"Ganesh Sankaralingam, Kanimozhi Subramaniyan, K Ezhilarasi, Dhamodharan Umapathy, Remya Rajan Renuka, MukeshKumar Dharmalingam Jothinathan, Shenbhagaraman Ramalingam","doi":"10.1007/s12032-025-02981-1","DOIUrl":"10.1007/s12032-025-02981-1","url":null,"abstract":"<p><p>Bendamustine, an alkylating agent used in treating hematological cancers like non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL), has recently garnered attention for its potential in breast cancer therapy. This study explores its anticancer effects and molecular mechanisms in breast cancer cells. MDA-MB-231 cells were exposed to various concentrations of bendamustine (0-50 µM), and cytotoxicity was assessed using Alamar Blue and LDH assays, revealing a dose-dependent reduction in cell viability with an IC₅₀ value of 16.98 μM at 24 h (p < 0.001). Intracellular reactive oxygen species (ROS) were quantified by DCF-DA flow cytometry, showing a significant elevation following treatment (p < 0.01). Downregulation of major antioxidant enzymes (SOD, CAT, GPx1, GST; p < 0.01) and upregulation of TRPC6 (1.8-fold at 10 μM, 2.5-fold at 20 μM; p < 0.01) were detected by qPCR. Markers of apoptosis were evaluated by Annexin V/PI staining, revealing significant increases in both early and late apoptotic cell populations (p < 0.01), and by gene expression analysis showing increased BAX:BCL-2 ratio (1.5-fold at 10 μM, 7.8-fold at 20 μM; p < 0.01). CHOP mRNA, an ER stress-related pro-apoptotic gene, was significantly upregulated (2.5-fold at 20 μM; p < 0.01), supporting activation of the ER stress pathway. The results demonstrated that bendamustine exerted a dose-dependent cytotoxic effect, decreasing cell viability and increasing LDH release. It significantly increased ROS levels and altered the expression of apoptotic genes, promoting apoptosis in breast cancer cells. Furthermore, bendamustine-induced ER stress, shown by upregulated Chop expression, suggests that ER stress plays a role in its anticancer activity. These findings highlight bendamustine as a promising therapeutic agent for breast cancer treatment.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 9","pages":"416"},"PeriodicalIF":3.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799564","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 mechanism of ncRNA in trastuzumab resistance in HER2-positive tumors.","authors":"Huan Zhao, Huihui Hu, Zhifei Li, Mengen Xu, Peipei Miao, Beibei Chen, Xiaobing Chen","doi":"10.1007/s12032-025-02976-y","DOIUrl":"10.1007/s12032-025-02976-y","url":null,"abstract":"<p><p>Human epidermal growth factor receptor-2 (HER2) is an essential biomarker in oncology. It is highly expressed in many tumors, especially in breast cancer and gastric cancer, and is associated with the malignant progression of tumors. Trastuzumab is a targeted drug for HER2-positive tumors, which can improve the efficacy of HER2-positive tumors, initiate precise treatment of HER2-positive tumors, and play an essential role in first-line therapy and second-line therapy. However, resistance to Trastuzumab is a limiting factor for its efficacy and a necessary factor for short patient survival and poor prognosis. The resistance mechanism to trastuzumab is complex, and non-coding RNA (ncRNA), a type of RNA that does not encode genes, mediates resistance, and plays important roles in of trastuzumab resistance. In clinical practice, ncRNA can be a biomarker for tumor progression, prognosis, and trastuzumab resistance. This article systematically summarizes the key mechanisms of ncRNA resistance to trastuzumab in HER2-positive tumors and its clinical application potential. Especially in this article, for the first time, ncRNA is integrated to regulate of trastuzumab resistance through epigenetic modification crosstalk, insulin-like growth factor 1 receptor (IGF1R) targets, exosome delivery, and ceRNA network regulation aimed to provide insights and references for basic research, drug development, and biomarker determination of trastuzumab resistance in HER2-positive tumors.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 9","pages":"415"},"PeriodicalIF":3.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799566","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":"Advanced nanotheranostic approaches for targeted glioblastoma treatment: a synergistic fusion of CRISPR-Cas gene editing, AI-driven tumor profiling, and BBB-modulation.","authors":"Chethan Patil, R Priyanka, B M Harshitha, S Oshik, S Yashwanth, B R Darshan, Shradha Patil, K A Prajwal, Prasiddhi Naik, Prakash Goudanavar, T Mallamma","doi":"10.1007/s12032-025-02944-6","DOIUrl":"10.1007/s12032-025-02944-6","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. It is hard to treat because it is very invasive, has a lot of genetic variation, and the blood-brain barrier (BBB) limits its growth. Traditional GBM treatments, including surgery, radiation and chemotherapy have only marginally improved survival requiring a paradigm shift. This review starts a new way of thinking about how to treat GBM by combining multi-responsive nanotheranostics, next-generation genome engineering, and AI-enabled stratification. The study compares smart nanocarriers that can transport payloads accurately and only when needed. CRISPR/Cas systems are useful for directly editing oncogenes, controlling GBM signaling cascades, making resistant cells sensitive again, and changing the ways that cells avoid the immune system. Nanoparticle-mediated CRISPR delivery and BBB disruption approaches, including targeted ultrasound, receptor-mediated transcytosis, and exosome-based delivery, could help get around the neuroprotective shield without damaging it. This review investigates the molecular aspects of the BBB, highlighting its dual role as a metabolic and efflux transporter-mediated barrier, and assesses cutting-edge nanocarrier systems, in particular hybrid exosome-nanoparticle designs, that aim to circumvent these limitations. Additionally, it explores the current limitations and possible future applications of gene editing tools and AI models for navigating the genomic instability and ever-changing tumor microenvironment of GBM. This study also discusses the ethical and legal issues related to these developing technologies, therefore stressing the need for clinically feasible, ethically controlled innovation pipelines. With an emphasis on cutting-edge research, this review delves into emerging areas such as nanotheranostics, cellular composition of GBM, CRISPR-based gene editing, AI-enabled precision medicine, and targeted disruption of the blood-brain barrier.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 9","pages":"413"},"PeriodicalIF":3.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794881","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":"Next-generation nanoformulation: Glycyrrhiza glabra-based chitosan-curcumin MgO/Fe₂O₃ nanocomposite for targeted lung cancer therapy with dual antioxidant action.","authors":"Alaa Elmetwalli, Sara Abdelsayed, Ashraf Elsayed, Mohammed S El-Hersh, Mervat G Hassan, Lamia A Gad, Medhat Ali Salah, Mohamed Basiouny Yahia, Mohamed A Shaheen, Mohamed F Ibrahim, Abdullah Mustafa Ibrahim, Hatem Mohamed Newish, Eman Alhomaidi, Ali H El-Far, Khaled M Elattar","doi":"10.1007/s12032-025-02977-x","DOIUrl":"10.1007/s12032-025-02977-x","url":null,"abstract":"<p><p>This study aims to develop and evaluate Glycyrrhiza glabra-based magnesium oxide/iron oxide nanocomposite (NC) functionalized with chitosan and curcumin to enhance therapeutic efficacy against lung cancer and oxidative stress. This is the first report integrating G. glabra extract with chitosan and curcumin functionalization into a MgO/Fe₂O₃ nanocomposite for enhanced antioxidant and anticancer effects. The developed nanocomposite demonstrated strong biocompatibility and in vitro therapeutic efficacy, as evidenced by low cytotoxicity in normal cells and significant inhibitory effects against A549 lung cancer cells. In this study, bioactive phytochemical-loaded G. glabra extract was used as a green capping and reducing agent to synthesize MgO/Fe₂O₃ NC. The nanomaterials were also functionalized with curcumin and chitosan to promote stability, bioavailability, and site-specific pharmacological activity. The synthesis process was carried out under green conditions, in which the nanocomposite was characterized using FTIR, UV-Vis spectroscopy, EDX analysis, zeta potential analysis, HR-TEM, and XRD. The antioxidant potential was assessed through the DPPH free radical scavenging activity, whereby MgO/Fe₂O₃-chitosan-curcumin NCs yielded the maximum inhibition of free radicals (IC₅₀ = 0.0977 mg/mL) when compared to other nanomaterials. Antimicrobial activity was assessed against Gram-negative and Gram-positive bacteria, wherein MgO/Fe₂O₃ NC showed moderate activity, and chitosan and curcumin functionalization reduced this to some extent by possibly controlled release behavior or protection of active sites. Cytotoxicity against A549 human lung cancer cells showed strong inhibition by the MgO/Fe₂O₃-chitosan-curcumin NC (IC₅₀ = 10 µg/mL), confirmed by changes in morphology in accordance with apoptosis. In addition, in silico ADME simulation suggested favorable bioavailability and low toxicity, which is an indicator of the therapeutic potential of these NCs. To the best of our knowledge, this is the first report on G. glabra-mediated green synthesis with dual functionalization of chitosan and curcumin in a MgO/Fe₂O₃ nanocomposite. The formulation has synergistic antioxidant and anticancer activity with vast potential in lung cancer therapy. As a whole, the findings address the dual antioxidant and anticancer properties of G. glabra-derived MgO/Fe₂O₃-chitosan-curcumin NC and their green potential as agents in the treatment of lung cancer. In vivo studies are recommended to confirm efficacy and safety.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 9","pages":"414"},"PeriodicalIF":3.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799565","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":"Evaluation of the efficacy and safety of HyperArc stereotactic radiotherapy for the treatment of lung cancer brain metastasis.","authors":"Yiyao Zhu, Zhifu Chen, Lihua Zhu, Tingjuan Zhang, Jun Chen, Yan Liu, Zhiyuan Qiu, Yan Wang, Chaoyang Wu","doi":"10.1007/s12032-025-02970-4","DOIUrl":"10.1007/s12032-025-02970-4","url":null,"abstract":"<p><p>This study assessed the efficacy and safety of HyperArc (HA) stereotactic radiotherapy (SRT) in 48 patients with lung cancer brain metastases (LCBM) while identifying prognostic factors and high-risk predictors for symptomatic cerebral radiation necrosis (sCRN). We enrolled 48 patients diagnosed with LCBM at the People's Hospital Affiliated to Jiangsu University between February 2021 and February 2025, assigning 44 to the SRT group and 4 to the WBRT-boost group. Clinical data were collected, and all patients underwent HA stereotactic radiotherapy. The WBRT-boost group additionally received a local HA boost. Prescription doses of 24-30 Gy were administered in 3-5 fractions at 5 fractions weekly, tailored to lesion characteristics. We evaluated both the efficacy and safety of HA treatment for LCBM. The 1-year overall survival (OS), intracranial distant progression-free survival (iDPFS), and intracranial local progression-free survival (iLPFS) rates for the entire cohort were 76.1, 64.5, and 69.4%, respectively. For out-of-field distant metastases, the cumulative intracranial objective response rate (icORR) and intracranial disease control rate (icDCR) reached 52.1 and 64.6%, compared with 81.2 and 97.9% for in-field metastases. The WBRT-boost group exhibited a median OS of 6.6 months, while the SRT group achieved superior 1-year outcomes (OS:79.1%; iDPFS:67.0%; iLPFS:71.8%). Compared with WBRT-boost, SRT showed significantly better local control (iLPFS, P = 0.044) and overall survival (OS, P = 0.036), though distant control (iDPFS, P = 0.086) did not differ significantly. Multivariate analysis identified V12 > 10 cc (HR 12.52, P = 0.011) and female sex (HR 11.66, P = 0.026) as independent prognostic factors. All 12 symptomatic radiation necrosis cases (27.3%) occurred in the SRT group. Logistic regression demonstrated that higher BED3 (HR 57.0, P = 0.009) independently increased sCRN risk, whereas targeted therapy (HR 0.08, P = 0.024) significantly reduced it. HyperArc-based fractionated stereotactic radiotherapy proves safe and feasible for managing brain metastases from lung cancer, achieving effective intracranial tumor control. Compared with WBRT + boost, SRT yields superior therapeutic outcomes despite requiring careful monitoring for symptomatic radiation necrosis. Further investigations should examine combined approaches incorporating targeted agents and optimized dose distribution.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 9","pages":"408"},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12328469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789469","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":"Impact of gastrointestinal dysbiosis on tryptophan metabolism and neurological cancer progression.","authors":"Neelakanta Sarvashiva Kiran, Chandrashekar Yashaswini, Ankita Chatterjee, Bhupendra Prajapati","doi":"10.1007/s12032-025-02972-2","DOIUrl":"10.1007/s12032-025-02972-2","url":null,"abstract":"<p><p>Gastrointestinal dysbiosis, characterized as a pathological imbalance in gut microbial composition and function, has been increasingly implicated in the aetiology of various systemic diseases, including neurological malignancies. This review illustrates the mechanistic link between dysbiosis and aberrant tryptophan metabolism, highlighting their convergence in the pathogenesis of neuro-oncological disorders. Tryptophan, a critical precursor for bioactive metabolites such as serotonin and kynurenine, undergoes extensive microbial and host-mediated catabolism. Dysbiosis disrupts these metabolic pathways, leading to altered neurotransmitter biosynthesis, heightened oxidative stress, dysregulated neuroinflammation, and perturbations in immune surveillance-all of which contribute to tumour initiation and progression within the central nervous system (CNS). Furthermore, dysregulated kynurenine pathway activation fosters an immunosuppressive tumour microenvironment (TME) through aryl hydrocarbon receptor (AhR) signalling, facilitating immune evasion and malignancy. The review systematically explores the molecular and cellular mechanisms by which gut microbial imbalances modulate tryptophan catabolism and its downstream effects on neuroimmune dynamics, oncogenic signalling cascades, and blood-brain barrier integrity. Emphasis is placed on emerging therapeutic strategies targeting the microbiota-tryptophan axis, including microbiome modulation, enzymatic inhibitors, and metabolic reprogramming approaches. By elucidating the crosstalk between gastrointestinal dysbiosis and tryptophan metabolism, we identify molecular entry points for intervention in neuro-oncology. Progress will require coordinated work across microbiology, immunology, oncology, and neurobiology to develop microbiome-targeted strategies for neurological malignancies.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 9","pages":"412"},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794883","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":"VAMP proteins: molecular architects in disease pathogenesis and therapeutic innovation.","authors":"Dongran Yu, Huhu Zhang, Xiaoyan Ding, Jingjing Guo, Lina Yang","doi":"10.1007/s12032-025-02969-x","DOIUrl":"10.1007/s12032-025-02969-x","url":null,"abstract":"<p><p>Vesicle-associated membrane protein is a widely distributed integral component within the human body, serving as a critical mediator of membrane fusion events in physiological and pathological processes. It contains a SNARE domain, an N-terminal hydrophilic structure and a C-terminal transmembrane domain. As emerging research evidence accumulates, VAMP proteins have been implicated in a diverse range of conditions, including various neoplastic diseases, as well as neurological and psychiatric disorders. Understanding its connection with tumors, which can serve as the foundation for molecular targeted therapies, is crucial for predicting tumor prognosis. Further investigation into the mutations and related pathway abnormalities of VAMP proteins will have a profound impact on the treatment of neurological and psychiatric diseases. This review systematically summarizes the structure, involved biological processes, immunotherapeutic methods, drug-targeted treatment strategies, biomarkers, mutation types, and related diseases of VAMP proteins. It aims to offer novel perspectives for the diagnosis and treatment of VAMP-associated diseases.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 9","pages":"411"},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794884","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":"Lipid nanoparticles: a promising tool for nucleic acid delivery in cancer immunotherapy.","authors":"Tasneem Abaza, Eman E Mohamed, Mohamed Y Zaky","doi":"10.1007/s12032-025-02939-3","DOIUrl":"10.1007/s12032-025-02939-3","url":null,"abstract":"<p><p>Cancer immunotherapy and nucleic acid therapy have demonstrated significant potential in reshaping cancer treatment paradigms. The combination of these therapeutic approaches offers promising prospects for enhancing systemic anti-tumor effects while minimizing adverse reactions commonly associated with traditional treatments. However, the clinical efficacy of these innovative therapies is often hindered by several delivery-related challenges. These include issues like degradation of therapeutic molecules, limited cellular uptake, the essential requirement for nuclear entry, and risks of off-target toxicity that can negatively impact patient safety. In this challenging landscape, nanoparticle delivery systems, particularly lipid nanoparticles (LNPs), have emerged as a groundbreaking solution to overcome these obstacles. LNPs facilitate the safe and efficient delivery of nucleic acid therapy directly to immune cells, enhancing their bioavailability and therapeutic impact. This review article examines the evolving role of LNPs in the landscape of cancer immunotherapy. Recent advancements in LNP-based nucleic acid delivery illustrate their potential to revolutionize the field by enabling precise modulation of gene expression and immune responses, paving the way for improved cancer treatment outcomes and providing a more effective arsenal against this complex disease.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 9","pages":"409"},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12328551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789470","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":"CAR T-cell immunotherapy as the next horizon in cancer eradication: current landscape, challenges, and future directions.","authors":"Hetvi Bharadia, Akshada Dabhade, Aayushi C Shah, Rajanikant Patel, Mehul R Chorawala, Artiben Patel, Palak A Shah","doi":"10.1007/s12032-025-02957-1","DOIUrl":"10.1007/s12032-025-02957-1","url":null,"abstract":"<p><p>Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a groundbreaking modality in cancer immunotherapy, offering remarkable clinical benefits, particularly in hematologic malignancies. By genetically reprogramming autologous T-cells to express synthetic receptors targeting tumor-specific antigens, CAR T-cells can mediate robust antitumor responses. This review provides a comprehensive overview of CAR T-cell immunotherapy, including its historical development, structural design, mechanism of action, and preclinical and clinical evolution. We highlight the intricacies of the tumor immune microenvironment, immune evasion mechanisms employed by cancer cells, and how CAR T-cells address these barriers. FDA-approved CAR T-cell therapies for B-cell malignancies and the current landscape of clinical trials for both liquid and solid tumors are critically analyzed. Furthermore, we explore novel targets, combination strategies, and technological innovations aimed at enhancing CAR T-cell efficacy and overcoming challenges related to antigen heterogeneity, toxicity, and resistance. Issues surrounding cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and tumor antigen escape are also discussed. The review delves into ongoing efforts in preclinical models, translational advancements, and emerging approaches such as dual-targeting CARs, armored CARs, and alternative co-stimulatory domains. Finally, the ethical, economic, and logistical challenges associated with CAR T-cell therapy are examined, including access disparities, manufacturing constraints, and the need for value-based pricing models. By synthesizing current insights and future directions, this review emphasizes transformative role of CAR T-cell therapy in oncology and the imperative for continued innovation to extend its benefits to broader patient populations.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 9","pages":"410"},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794882","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}