Cancer Genetics and Epigenetics 2025, Vol.13 http://medscipublisher.com/index.php/cge © 2025 MedSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved.
Cancer Genetics and Epigenetics 2025, Vol.13 http://medscipublisher.com/index.php/cge © 2025 MedSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. MedSci Publisher is an international Open Access publisher specializing in cancer genetics, cancer epigenetics, clinical pharmacology, cancer biology at the publishing platform that is operated by Sophia Publishing Group (SPG), founded in British Columbia of Canada. Publisher MedSci Publisher Editedby Editorial Team of Cancer Genetics and Epigenetics Email: edit@cge.medscipublisher.com Website: http://medscipublisher.com/index.php/cge Address: 11388 Stevenston Hwy, PO Box 96016, Richmond, V7A 5J5, British Columbia Canada Cancer Genetics and Epigenetics (ISSN 2369-2995) is an open access, peer reviewed journal published online by MedSci Publisher. The journal is aimed to publish all works in the areas that with quality and originality, with a scope that spans the areas of cancer genetics and cancer epigenetics. It is archived in LAC (Library and Archives Canada) and deposited in CrossRef. The journal has been indexed by ProQuest as well, expected to be indexed by PubMed and other datebases in near future. All the articles published in Cancer Genetics and Epigenetics are Open Access, and are distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. MedSci Publisher uses CrossCheck service to identify academic plagiarism through the world’s leading plagiarism prevention tool, iParadigms, and to protect the original authors’ copyrights.
Cancer Genetics and Epigenetics (online), 2025, Vol. 13, No. 5 ISSN 2369-2995 http://medscipublisher.com/index.php/cge © 2025 MedSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. Latest Content Bottlenecks and Breakthrough Pathways of CAR-T Cell Therapy in Solid Tumors ManmanLi Cancer Genetics and Epigenetics, 2025, Vol. 13, No. 5, 206-214 Comparison and Optimization Pathways of End-of-Life Care Nursing Models for Advanced Cancer Patients JieWang Cancer Genetics and Epigenetics, 2025, Vol. 13, No. 5, 215-223 The Effect of App-or Remote Monitoring-Based Digital Health Tools on Cancer Patients’ Quality of Life Sufu Lü, Jianhui Li Cancer Genetics and Epigenetics, 2025, Vol. 13, No. 5, 224-235 Correlation Analysis of Postoperative Recurrence in Hepatocellular Carcinoma Patients and the Dynamic Evolution of the Tumor Immune Microenvironment Qiyan Lou, Xiaoying Xu Cancer Genetics and Epigenetics, 2025, Vol. 13, No. 5, 236-244 Nursing Interventions and Evaluation of Social Function Recovery in Young Breast Cancer Patients Returning to Society After Surgery Jianmin Liu Cancer Genetics and Epigenetics, 2025, Vol. 13, No. 5, 245-253
Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 206-214 http://medscipublisher.com/index.php/cge 206 Systematic Review Open Access Bottlenecks and Breakthrough Pathways of CAR-T Cell Therapy in Solid Tumors ManmanLi Hainan Institute of Biotechnology, Haikou, 570206, Hainan, China Corresponding email: manman.li@hibio.org Cancer Genetics and Epigenetics, 2025, Vol.13, No.5 doi: 10.5376/cge.2025.13.0021 Received: 08 Jul., 2025 Accepted: 10 Aug., 2025 Published: 13 Sep., 2025 Copyright © 2025 Li, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Li M.M., 2025, Bottlenecks and breakthrough pathways of CAR-T cell therapy in solid tumors, Cancer Genetics and Epigenetics, 13(5): 206-214 (doi: 10.5376/cge.2025.13.0021) Abstract This study explored the main challenges and coping strategies of CAR-T cell therapy in the treatment of solid tumors. Although this therapy has shown remarkable efficacy in hematological malignancies, it still faces many limitations in solid tumors, including the lack of tumor-specific antigens, antigen heterogeneity and immunosuppressive microenvironment, which lead to insufficient infiltration, easy depletion and poor persistence of CAR-T cells. To this end, current research is dedicated to developing multi-target and logic-gated cars, novel antigen discovery, armored CAR-T combined immune checkpoint inhibitors, and enhancing the chemotaxis, metabolic adaptation and long-term survival ability of CAR-T cells through genetic engineering. Clinical trials have observed remission in some patients, but the overall efficacy remains limited, and there are risks such as cytokine release syndrome and neurotoxicity. Future research will focus on interdisciplinary integration (such as CAR-NK, TCR-T), synthetic biology-driven intelligent controllable CAR design, and individualized precision treatment based on genomic and tumor heterogeneity, in order to promote clinical transformation and expand its application. Keywords CAR-T cell therapy; Solid tumors; Tumor microenvironment (TME); Antigen heterogeneity; Precision medicine 1 Introduction CAR-T cell therapy has achieved excellent results in the treatment of hematological malignancies by modifying T cells to carry chimeric antigen receptors capable of recognizing tumor antigens. The FDA-approved CAR-T therapy related to CD19 and BCMA has shown good therapeutic effects in patients with B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma and multiple myeloma. Even for patients who have no effect with traditional methods, significant improvement in their condition can be observed (Dagar et al., 2023; Khan et al., 2025). This success is mainly due to the relatively uniform distribution of target antigens in hematological malignancies, which makes it easier for CAR-T cells to locate and eliminate cancer cells. CAR-T therapy has become an important breakthrough in this field (Wagner et al., 2020; Chen et al., 2024). The application of CAR-T therapy in the treatment of solid tumors still faces many difficulties. The main difficulties include the absence of highly specific tumor antigens, different antigen expression conditions, and the possibility of targeting non-tumor tissues, which can lead CAR-T cells to attack normal tissues. In addition, the tumor microenvironment with immunosuppressive effects, physical obstacles, and the insufficient number of T cells entering the tumor also greatly limit the therapeutic effect (Knochelmann et al., 2018; Khan et al., 2025). Current early clinical trials have shown that the therapeutic effect of CAR-T therapy in solid tumors is relatively limited, unstable, and there are obvious safety issues, such as cytokine release syndrome and neurotoxicity (Marofi et al., 2021; Ai et al., 2024; Tony et al., 2025). This study will explore how to expand the application scope of CAR-T cell therapy in patients with solid tumors through precise tumor treatment strategies, and systematically analyze the key issues therein. The key contents include the design of the new-generation CAR structure, the screening of tumor-specific antigens, the implementation of combined treatment strategies, and the regulatory mechanism of the tumor microenvironment. This study aims to provide theoretical and practical support for improving the sustained efficacy, safety and application scope of CAR-T therapy by comprehensively evaluating the existing progress and challenges in these aspects, and to promote the establishment of a more effective and personalized cancer immunotherapy system.
Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 206-214 http://medscipublisher.com/index.php/cge 207 2 An Overview of the Development of CAR-T Cell Therapy 2.1 Structure and evolution Since its emergence, the structure of chimeric antigen receptor (CAR) T-cell therapy has undergone significant changes. The first-generation CAR was composed of a single-stranded variable fragment (scFv) for recognizing antigens and connecting to the CD3ζ signaling region to provide an initial activation signal, but its duration and effect were not satisfactory. The second-generation CAR incorporates a single co-stimulatory region (such as CD28 or 4-1BB), significantly enhancing the proliferation, survival and tumor clearance ability of T cells, laying an important foundation for the treatment of blood cancers (Marofi et al., 2021; Chen et al., 2024; Khan et al., 2025). The subsequent generations of cars have all been continuously improved on the basis of the previous generation. The third-generation CAR combines multiple auxiliary stimulus structures, enhancing the activity and continuous functioning ability of T cells. The fourth-generation "armored" CAR has been modified to secrete cytokines or resist immunosuppressive effects, thus performing better in complex tumor environments. The fifth-generation CAR incorporates components of cytokine receptor signaling, which can more accurately regulate the activation and reproduction of T cells and enhance their adaptability in the immunosuppressive environment of solid tumors (Chen et al., 2024; Li, 2024). The progress of research indicates that people have gained a deeper understanding of T cells and tumor immunity. The design of the new generation of cars should strive to address issues such as multiple antigens and the decline in T cell function (Wagner et al., 2020; Albelda, 2023; Ai et al., 2024). 2.2 Successful experience CAR-T cell therapy has a good therapeutic effect in hematological malignancies. In the treatment of B-cell acute lymphoblastic leukemia targeting CD19, diffuse large B-cell lymphoma, and multiple myeloma targeting BCMA, even if patients do not respond well to conventional treatments, CAR-T therapy can still bring relatively good therapeutic effects and help control the condition. These good results are mainly due to the relatively stable target antigens on the surface of tumor cells, making it easier for CAR-T cells to find and eliminate cancer cells in the blood environment (Chen et al., 2024; Khan et al., 2025). The FDA-approved related products, such as Kymriah and Yescarta for the treatment of CD19-positive cancers, and idecabtagene vicleucel for the treatment of BCMA-positive myeloma, all demonstrate the clinical value of this treatment strategy. These treatment methods have redefined the standards for personalized tumor treatment, demonstrating that even if other treatments are ineffective, the modified T cells can still achieve long-term disease control (Wagner et al., 2020; Dagar et al., 2023). The experience summarized from these successful cases provides an important reference for the expansion of CAR-T technology to the research of solid tumors. 2.3 Limitations and implications Although CAR-T performs well in hematological malignancies, its application in solid tumors still faces many difficulties. The main problems include the lack of highly specific tumor antigens, the diversity of antigen expression, and the existence of inhibitory tumor microenvironments, all of which will affect the recognition, entry and sustained action of CAR-T cells on tumors (Chen et al., 2024; Khan et al., 2025). In addition, safety risks such as off-target toxicity and cytokine release syndrome remain difficult issues that need to be taken seriously. Based on the clinical experience in treating blood diseases, it is very important to select the appropriate antigen, ensure that T cells can increase effectively, and handle the side effects that occur properly. For solid tumors, to address issues such as interstitial blockage, hypoxia, and immunosuppression, it is necessary to design more advanced CAR structures, improve the methods for recognizing antigens, and explore the path of combined therapy. These practices are driving the development of more precise CAR-T cell products and new clinical protocols, with the aim of benefiting more cancer patients (Wagner et al., 2020; Ai et al., 2024; Tony et al., 2025). 3 Major Bottlenecks of CAR-T Cell therapy for Solid Tumors 3.1 Target limitation One of the main challenges of CAR-T therapy in treating solid tumors is the inability to recognize antigens that
Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 206-214 http://medscipublisher.com/index.php/cge 208 are only present on solid tumors. Unlike blood cancers (for instance, CD19 mainly appears on cancer cells), the antigens of most solid tumors also exist in small amounts in normal tissues. This situation of antigen overlap increases the risk of accidental injury to normal tissues. CAR-T cells may attack healthy cells, causing severe and even life-threatening side effects (Yan et al., 2023; Tony et al., 2025). In addition, due to the different expression of antigens within the same tumor or among different patients, some cancer cells cannot be recognized, making it difficult to completely eliminate the tumor and eventually causing disease recurrence (Dagar et al., 2023; Guzman et al., 2023; Khan et al., 2025). To address these issues, researchers are designing new types of CAR-T cells, such as CAR-T cells capable of targeting multiple targets or those with logical control. Before these new CAR-T cells are activated, they need to recognize two or more antigens simultaneously. This can improve the accuracy of recognition and also reduce toxic side effects. But at present, it is still very difficult to find the ideal combination of antigens. Meanwhile, tumor cells may evade the action of CAR-T cells by reducing or removing target antigens. This requires continuous optimization of antigen selection and CAR design (Rodríguez-García et al., 2020; Sorkhabi et al., 2023; Chen et al., 2024). 3.2 Tumor microenvironment inhibition The microenvironment (TME) within solid tumors is highly immunosuppressive, severely limiting the efficacy of CAR-T cells. Among them, regulatory T cells, myeloid-derived suppressor cells and tumor-associated macrophages, etc. will release inhibitory cytokines (such as TGF-β, IL-10), hindering the activation and proliferation of CAR-T cells (Figure 1) (Fonkoua et al., 2022; Sorkhabi et al., 2023; Ai et al., 2024). Meanwhile, the TME is usually hypoxic, acidic and nutritionally deficient, all of which can weaken the metabolism and function of T cells (Marofi et al., 2021; Maalej et al., 2023; Chen et al., 2024). Figure 1 CAR-T structure modification to enhance killing potential (Adopted from Ai et al., 2024) Physical obstacles such as dense and thick extracellular matrix and abnormal vascular structure can also prevent CAR-T cells from entering tumor tissues and affect their activity in tumor tissues. These factors together create an unfavorable environment for treatment, not only restricting the contact between CAR-T cells and tumors, but also accelerating the process of CAR-T cell function weakening and loss of efficacy. The current methods for dealing with this microenvironment include: modifying CAR-T cells to secrete inflammatory factors, resist inhibitory
Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 206-214 http://medscipublisher.com/index.php/cge 209 signals, or produce enzymes capable of decomposing extracellular matrix (Hou et al. 2021; Dagar et al., 2023; Khan et al., 2025). 3.3 T cell dysfunction CAR-T cells face multiple functional difficulties in the treatment of solid tumors: they are difficult to migrate to the tumor area, difficult to cross the physicochemical barrier and immune barrier, and prone to rapid exhaustion. Unlike malignant cells in hematological malignancies that are easily accessible, solid tumors require CAR-T cells to cross complex tissue structures and resist inhibitory signals before reaching the target site (Marofi et al., 2021; Maalej et al., 2023; Dagar et al., 2023; Khan et al., 2025). After CAR-T cells enter the tumor, they often gradually lose their function due to continuous antigen stimulation, manifested as reduced cytokine secretion, decreased killing ability and increased inhibitory receptors. This weakened function, coupled with the lack of supporting factors and long-term immunosuppression, shortens the survival time of CAR-T cells and makes it difficult to maintain the anti-tumor effect. The coping methods include optimizing the signal structure of CAR, combining the use of checkpoint inhibitors, or enhancing the metabolic level of T cells and their ability to resist functional decline through genetic modification (Sorkhabi et al., 2023; Ai et al., 2024; Chen et al., 2024). 4 Breakthrough Approaches and Cutting-edge Strategies for CAR-T Cell Therapy 4.1 Design exploration of novel solid tumor antigens and multi-target cars Researchers are developing CAR-T cells capable of recognizing multiple antigens to address the issue of uneven antigen distribution and the lack of truly specific targets in solid tumors. Bispecific or tandem cars can simultaneously bind to two or more antigens, which can reduce tumor escape caused by antigen absence and expand the range of tumor cell recognition. By simultaneously locking multiple tumor-related antigens, these novel CAR structures can more accurately identify tumors and reduce accidental damage to normal tissues-which is a very important safety issue in the treatment of solid tumors (Figure 2) (Dagar et al., 2023; Sorkhabi et al., 2023; Yan et al., 2023; Chen et al., 2024). Meanwhile, by means of high-throughput screening, single-cell sequencing and artificial intelligence, scientists are striving to search for new solid tumor antigens, including tumor-specific antigens (TSA) and neoantigens (Yan et al., 2023). The discovery of neoantigens specific to tumor cells is conducive to the development of safer and more potent CAR-T therapies, benefiting more patients with solid tumors (Guzman et al., 2023; Khan et al., 2025). 4.2 Armored CAR-T and its combined application with immune checkpoint inhibitors The immunosuppressive characteristics of the tumor microenvironment (TME) are the main difficulty faced by CAR-T in the treatment of solid tumors. The modified armored CAR-T cells can secrete pro-inflammatory cytokines (such as IL-12, IL-18) or express receptors that can block inhibitory signals, thereby enhancing the viability and survival ability of T cells in the TME (Fonkoua et al., 2022; Sorkhabi et al., 2023). These modifications enable CAR-T cells to resist the influence of regulatory cells and inhibitory factors, enhancing their tumor-clearing effect (Marofi et al., 2021; Chen et al., 2024). The combination of CAR-T therapy and immune checkpoint suppressor drugs (such as anti-PD-1 and anti-CTLA-4 antibodies). This combined approach can reactivate T cells that have lost their function and also interfere with the immunosuppressive pathways in the TME. Thus, CAR-T cells can survive for a longer time and enhance their function at the same time (Fonkoua et al., 2022). Early clinical and preclinical research results have shown that this combination therapy can have a synergistic enhanced anti-cancer effect on solid tumors (Khan et al., 2025; Lou and Xu, 2025). 4.3 Improve chemotaxis, metabolism and persistence through genetic engineering Genetic engineering is used to enhance the migration, metabolic adaptation and long-term persistence of CAR-T cells in solid tumors. By introducing receptors that match the chemokines released by tumors (such as CXCR2,
Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 206-214 http://medscipublisher.com/index.php/cge 210 CCR2), CAR-T cells can be guided into the tumor interior more effectively, overcoming the obstacle of their difficulty in infiltration. Furthermore, enhancing the resistance of cells to hypoxia and nutritional deficiency helps CAR-T maintain normal function in severe TME (Martinez and Moon, 2019; Sorkhabi et al., 2023; Ai et al., 2024; Khan et al., 2025). Figure 2 CAR-T cell therapy challenges and their mitigation strategies (Adopted from Dagar et al., 2023) Image caption: A: Cytokine Release Syndrome (CRS) (1): Choice of costimulatory domain CD28 or 41BB as well as the length of the hinge domain influence CRS (2) Cytokines released by macrophages and Inflammatory cytokines and immunostimulatory alarmins released during pyroptosis can be mitigated by using specific drugs for each cytokine (e.g., Etanecerpt, Tocilizumab, Corticosteroids, Dasatinib, Emapalumab); B: Tumor-associated antigen escape: (1): CAR-T cell-mediated killing of target cell if the target antigen is present on the surface (2): Tumor antigen escape in the absence of surface antigen of the CAR-T cell and potential strategies to abet it by using DUAL CARs and BiTE CARs; C: Trafficking and tumor infiltration: (1): Schematic diagram to demonstrate reduced homing of CAR-T cells to tumor microenvironments due to the presence of different cellular components; (2): Improving homing of CAR-T cells to TME by using armored anti-angiogenic CARs as well as self-driving CARs, which express multiple anti-angiogenic factors; D: On-target Off-tumor/Lack of reliable TAAs; Schematic diagram to demonstrate targeting of the normal cell by CAR-T cells if the antigen is expressed on normal cells, which can be mitigated by a selection of reliable tumor-associated antigen by integration of artificial intelligence with big data mining; E: Immunosuppressive tumor microenvironment: (1): Diagram to illustrate suppressive tumor microenvironment comprising different cellular components including low oxygen, cancer-associated fibroblast, high ROS and other components that diminish proliferation of CAR-T cells; (2): CAR-T expressing anti-checkpoint inhibitors to promote the growth of T cells in tumor microenvironments; (3) HIF1α-inducible CARs, which get activated in hypoxic tumor microenvironment. HIF1α to promote T cell growth; (4): Catalase-expressing CAR to scavenge reactive oxygen species in tumors to promote T cell growth. CARs, Chimeric antigen receptors; BiTE, bispecific T-cell engagers; TAAs: Rumor-associated antigens; TME: Tumor microenvironment; ROS: Reactive oxygen species; HIF1α: Hypoxia inducible factor 1 alpha (Adopted from Dagar et al., 2023) The methods to increase the survival time of CAR-T cells include improving the co-stimulatory signal, using checkpoint inhibition to alleviate T cell fatigue, and modifying cells to avoid cell death and delay aging. The common goal of these improvements is to maintain the activity and function of CAR-T cells for a longer period of time, thereby increasing the probability of long-term control of solid tumors (Sorkhabi et al., 2023; Chen et al., 2024; Han et al., 2025; Zhu et al., 2025). 5 Clinical Study and Application of CAR-T Cell Therapy 5.1 Representative clinical trials Multiple clinical trials have tested the efficacy of CAR-T cell therapy against various solid tumor antigens, such as
Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 206-214 http://medscipublisher.com/index.php/cge 211 HER2, Claudin18.2 and GD2. Studies targeting HER2 have been carried out in sarcoma and glioblastoma. CAR-T targeting Claudin18.2 has been tested in gastrointestinal cancers, while CAR-T targeting GD2 has shown certain effects in neuroblastoma and other childhood solid tumors (Tony et al., 2025). Although the types of targets are diverse, most trials still use first-generation or second-generation CAR-T products, and there are still relatively few next-generation structures entering clinical evaluation (Sorkhabi et al., 2023; Chen et al., 2024). Worldwide, the number of related clinical trials is constantly increasing, among which China and the United States are leading in the number of studies. Now, more than 40 different antigens have been studied, which indicates that people are constantly seeking ideal targets for solid tumors. However, most of these trials are still at an early stage, mainly focusing on safety and feasibility studies, and have not shown obvious therapeutic effects yet (Sterner and Sterner, 2021; Guzman et al., 2023). 5.2 The partial remission and overall therapeutic effect of the patient remain unsatisfactory Although in some trials, the conditions of some patients have partially improved or no longer deteriorated, the overall effect of CAR-T treatment for solid tumors is still not very satisfactory. Compared with the obvious remission effect in the treatment of blood cancer, the remission of solid tumors often lasts for a short time and has limited effect, and complete remission cases are even rarest (Misawa et al., 2022; Sorkhabi et al., 2023). The reasons for this result include different antigen expressions, weak T cells' ability to enter tumors, and the inhibitory effect of the tumor microenvironment. These circumstances indicate that the design of CAR-T cells still needs further improvement, the method of selecting patients still needs to be refined, and the formulation of combined treatment plans also needs to further enhance the therapeutic effect. The current research focuses include developing new-generation Cars, multi-target strategies and adjuvant therapeutic approaches to overcome existing obstacles and bring more durable therapeutic effects to patients with solid tumors (Guzman et al., 2023; Chen et al., 2024; Khan et al., 2025; Tony et al., 2025). 5.3 Cytokine release syndrome, neurotoxicity and other adverse events The safety of CAR-T treatment for solid tumors still requires high attention. Cytokine release syndrome (CRS) and neurotoxicity are well known in the treatment of hematological malignancies and occur from time to time in solid tumor trials, sometimes leading to serious and even life-threatening consequences (Sorkhabi et al., 2023; Chen et al., 2024; Khan et al., 2025). Since the target antigen is also expressed in normal tissues, off-target toxicity is particularly worthy of attention, which may cause adverse reactions, limit the dosage of medication and affect the therapeutic effect. To reduce these risks, the current measures adopted include adding safety switches, optimizing antigen selection and strengthening patient monitoring. However, how to balance the therapeutic effect and safety remains a major challenge, which also indicates that CAR-T cell modification technology and clinical management need continuous innovation (Dimitri et al., 2022; Guzman et al., 2023; Yan et al., 2023). 6 Future Prospects: CAR-T Cell Therapy for Solid Tumors 6.1 It can be used in combination with adoptive cell therapies such as CAR-NK and TCR-T Combining CAR-T cell therapy with other adoptive cell treatment methods, such as CAR-NK (chimeric antigen receptor natural killer cells) and TCR-T (T cell receptor engineered T cells), is a promising direction for addressing the problems existing in CAR-T treatment of solid tumors. CAR-NK cells have many advantages. For instance, they do not rely on HLA when identifying tumors, have a relatively low risk of triggering graft-versus-host disease, and may be easier to obtain. These characteristics make it very attractive in combination therapy or alternative treatment regimens for solid tumors (Larson et al., 2022). TCR-T cells can recognize intracellular antigens presented by MHC molecules, make up for the deficiencies of CAR-T, expand the targeting range of tumor antigens, and deal with different tumor types (Maalej et al., 2023; Chen et al., 2024). When these methods are used together, they can solve the problem of tumor drug resistance through their respective different ways of action, thereby improving the therapeutic effect. For instance, CAR-NK and CAR-M
Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 206-214 http://medscipublisher.com/index.php/cge 212 (CAR-macrophage) therapies are currently under study. They can help CAR-T better enter solid tumors, improve the tumor microenvironment, and also deliver antigens to T cells. When used in combination with CAR-T, they are expected to exert stronger effects. This combination of multiple methods not only increases the treatment options but also brings more hope to the treatment of patients with solid tumors (Zhang et al., 2022). 6.2 Application of smart switches and adjustable CAR designs The field of synthetic biology is driving CAR-T cell therapy into a new stage of development, mainly through the use of smart switches and adjustable CAR structures. These methods can precisely control the activation, functional maintenance and safety of CAR-T cells, thereby addressing key issues such as the toxicity of accidental damage to normal cells and cytokine release responses (Chen et al., 2024). Intelligent switches include gene switches that can trigger cell suicide, as well as CAR-T cells controlled by small molecules. With the help of these switches, doctors can adjust the activity of CAR-T cells in real time, thereby improving the flexibility and safety of treatment (Tony et al., 2025). The CAR design using logic control and synthetic circuits requires the joint activation of multiple signals to enhance tumor specificity and reduce damage to normal tissues (Ma et al., 2019; Khan et al., 2025). These synthetic biology tools are expected to make CAR-T therapy safer, easier to manage, and better adapted to the complex environment of solid tumors. 6.3 Combining genomics with tumor heterogeneity analysis Personalized and precision medicine is gradually being integrated into the research of CAR-T cell therapy. Genomics and single-cell sequencing technologies can help discover patient-specific tumor antigens and analyze different tumor types, which is of great value for designing more effective and personalized CAR-T products (Chen et al., 2024). Researchers hope to customize CAR-T therapy based on the unique molecular characteristics of patients' tumors, thereby enhancing the accuracy of targeting and therapeutic effects. Combining multi-omics data with artificial intelligence can better infer the expression of antigens and the causes of drug resistance, thereby selecting the most suitable CAR design for different patients (Dagar et al., 2023; Khan et al., 2025). This approach tailored to individual circumstances is expected to enhance clinical treatment outcomes while reducing side effects, marking a significant step forward for solid tumor immunotherapy towards precise tumor treatment. 7 Concluding Remarks CAR-T cell therapy for solid tumors still faces persistent challenges, mainly due to the lack of specific antigens that truly exist only within tumors. As a result, it is difficult to accurately identify tumors and minimize damage to normal tissues. The tumor microenvironment (TME) with inhibitory effects can also seriously affect the treatment outcome. It will prevent T cells from entering tumors, accelerate the rate at which T cells lose their function, and also create metabolic and physical obstacles, restricting the survival and functioning of CAR-T cells. The combination of these factors leads to the relatively poor effect of CAR-T in combating tumors, which also indicates that new methods are urgently needed now to enable CAR-T to fully play its role in the treatment of solid tumors. To address these challenges, researchers are developing CAR designs capable of recognizing multiple antigens to tackle the problems of different tumor antigen types and tumor evasion of recognition. At the same time, CAR-T with "protective effects" will also be adopted, or it will be used in combination with checkpoint inhibitors and other methods to regulate the TME, in order to combat immunosuppression and prolong the time for T cells to function. The methods of combined therapy are also under study, such as combining CAR-T with other cell therapies (like CAR-NK, TCR-T) or conventional treatments. These methods are expected to jointly enhance the therapeutic effect and safety, providing patients with solid tumors with more durable and effective treatment responses. In the future, CAR-T treatment for solid tumors will place greater emphasis on precise treatment based on
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Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 215-223 http://medscipublisher.com/index.php/cge 215 Systematic Review Open Access Comparison and Optimization Pathways of End-of-Life Care Nursing Models for Advanced Cancer Patients JieWang Zhuji People’s Hospital, Zhuji, 311800, Zhejing, China Corresponding email: 2308763906@qq.com Cancer Genetics and Epigenetics, 2025, Vol.13, No.5 doi: 10.5376/cge.2025.13.0022 Received: 13 Jul., 2025 Accepted: 18 Aug., 2025 Published: 30 Sep., 2025 Copyright © 2025 Wang, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Wang J., 2025, Comparison and optimization pathways of end-of-life care nursing models for advanced cancer patients, Cancer Genetics and Epigenetics, 13(5): 215-223 (doi: 10.5376/cge.2025.13.0022) Abstract This study explores several hospice care approaches for patients with advanced cancer, including hospital/hospice ward care, home and community care, as well as multidisciplinary team collaboration models. Research has found that the care methods in hospitals and hospice wards can enable patients to quickly access medical resources and effectively control symptoms, but they may lead to problems such as over-treatment and insufficient personalized care. Family and community care can enable patients to receive care in a familiar environment and achieve a "good death", but it is often affected by insufficient resources and inadequate support from caregivers. The multidisciplinary and nurse-led model is significantly more effective in alleviating symptoms, maintaining mental health, and enhancing family satisfaction. The article also points out the current problems existing in hospice care, such as lack of resources, insufficient policy support, inadequate professional capabilities, and cultural obstacles. To optimize end-of-life care in the future, it is necessary to enhance policy and insurance support, promote the integration of medical care and nursing as well as multi-disciplinary cooperation, improve the professional training system, and raise public awareness of end-of-life care. Only in this way can patient-centered, comprehensive and high-quality end-of-life care services be achieved. Keywords End-of-life care; Advanced cancer patients; Nursing models; Multidisciplinary collaboration; Optimization pathways 1 Introduction The number of patients with advanced cancer worldwide has been increasing, especially among the elderly. It is predicted that in the coming years, up to 70% of cancer patients may occur in people aged 65 and above. As the survival conditions of many patients with advanced cancer have not changed much, people have begun to pay more attention to improving the quality of life and ensuring that patients can complete their last days with dignity and comfort. EoL care is of great significance in meeting the complex physical, psychological, social and spiritual needs of patients and their families. Its aim is to offer comfort, alleviate symptoms and provide assistance to patients in their final stages of life (Ghezelsefli et al., 2020). Recent research indicates that nurses and multidisciplinary teams play a crucial role in providing effective EoL care to patients with advanced cancer. From nurse-led multidisciplinary hospice care to more advanced nursing interventions, various nursing models have been proven to improve the quality of life of patients, enhance emotional health, and make patients more satisfied with nursing (Liu et al., 2024; Useck-Guerrero et al., 2024). A comprehensive care approach that combines psychological, spiritual and educational support is increasingly regarded as a good practice. It has also been proven that integrating palliative care with advance care planning earlier can reduce excessive treatment intervention and make care in line with the patient's wishes (Lin et al., 2018; Hua et al., 2024). However, problems still exist, such as the inconsistent definition of EoL, different nursing models, and deficiencies in nurse education and support (Crawford et al., 2021;Terzi and Kapucu, 2022; Jeong et al., 2023). This study will comparatively analyze the existing EoL care models for patients with advanced cancer, assess the effectiveness of these models, and identify optimization directions for future care practices. This study aims to introduce the current nursing models and their effects, analyze multidisciplinary and nurse-led nursing interventions, discuss the difficulties encountered in doing EoL nursing well and the factors that can be helpful,
Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 215-223 http://medscipublisher.com/index.php/cge 216 and put forward suggestions on combining scientifically based strategies to improve the end-of-life experience of patients and their families. 2 Overview of Hospice Care for Patients with Advanced Cancer 2.1 Definition and core concepts of hospice care Hospice care for patients with advanced cancer refers to the care provided in the last few weeks or months of their lives. At this point, as the patient's condition worsens and their health deteriorates rapidly, they are getting closer and closer to death. Its main goal is to make patients feel comfortable and improve their quality of life as much as possible. The focus of care has shifted from treating diseases to comprehensive care centered on patients, addressing their physical, psychological, social and spiritual needs. This nursing approach emphasizes alleviating symptoms, halting unnecessary treatment interventions, and formulating personalized care plans based on the patient's condition. Usually, supportive care and palliative care need to be incorporated as early as possible during the tumor treatment process (Levoy et al., 2023). EoL care adheres to the principle of "comprehensive care", taking into account the connections among physical, emotional, social and mental health. It is comprehensive and patient-centered, focusing on the comfort and dignity of patients when they are on the verge of death. Effective EoL care also involves clear communication with patients and their families, such as discussing care goals, available care options, and shifting from disease-treating care to care centered on patient comfort (Lin et al., 2018; Crawford et al., 2021). 2.2 Main nursing needs of patients with advanced cancer Patients with advanced cancer have complex and multi-faceted needs towards the end of their lives. Physically, they usually need to enhance the management of pain, breathing difficulties, fatigue and other uncomfortable symptoms (Crawford et al., 2021). Psychologically, patients may experience anxiety, depression, and the pain of survival, which requires strong psychological support and methods to help them adapt to and accept the current situation (Liu et al., 2024). In terms of society, the participation of family members and caregivers, the coordination of care work, and supportive interaction are of great significance, as they can address patients' loneliness and promote communication among each other (Ghezelsefli et al., 2020; Terzi and Kapucu, 2022; Trakoolngamden et al., 2025). The spiritual needs are also prominent, as patients, towards the end of their lives, seek the meaning of life, inner peace and acceptance of death. Mental support can help patients and their families solve problems related to survival and give them a sense of "passing away peacefully" (Gao et al., 2025). Comprehensive care models that integrate all the above needs, such as multi-disciplinary team care led by nurses and hospice care programs, can improve the quality of life of patients, reduce negative emotions, and make patients and their families more satisfied (Liu et al., 2024; Usech-guerrero et al., 2024). 2.3 The unique value of hospice care in tumor care Oncology nurses play a very crucial role in providing EoL care. They are supporters, knowledge explainers and care coordinators for patients and their families. Nurses have a lot of contact with patients and can always pay attention to their conditions, handle symptoms and provide emotional support. Professional education and training, such as hospice care training and cosmetic care training, have been proven to enhance nurses' confidence, job performance and awareness of EoL care, especially in physical and psychological care (Jeong et al., 2023; Shahmohammadi et al., 2024) Experienced practicing nurses focus on pain control, suggest formulating care plans as early as possible, assist patients in self-management, and encourage family members to join in, thereby enhancing the effectiveness of care. Integrating cancer care knowledge into teamwork can alleviate symptoms more effectively, increase the satisfaction of patients and caregivers, and improve the quality of life of patients at the end of their lives (Crawford et al., 2021; Liu et al., 2024; Usech-guerrero et al., 2024). The all-round care approach of cancer nurses and their ability to build mutual trust with patients and their families are key factors in providing high-quality end-of-life care.
Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 215-223 http://medscipublisher.com/index.php/cge 217 3 Comparison of End-of-life Care Models for Patients with Advanced Cancer 3.1 Based on the hospital and hospice ward model The practice based on hospitals and hospice wards is the traditional approach to caring for patients with advanced cancer, usually carried out in specialized departments or hospice wards. Such places have more abundant medical resources, which can better control symptoms, continuously monitor the condition, and respond promptly when the condition suddenly changes. Studies have shown that multidisciplinary palliative teams in hospitals and hospice care institutions contribute to strengthening symptom management, enhancing the satisfaction of patients and their families, and providing more adequate psychological support, especially in the last few weeks and days of life (Figure 1) (Crawford et al., 2021; Hua et al., 2024). However, aggressive treatment and repeated hospitalizations remain relatively common, sometimes making it difficult for care to meet patients' expectations of comfort and dignity (Koroukian et al., 2023; Kwon et al., 2025). Figure 1 Total care of the adult cancer patient at the end of life (Adopted from Crawford et al., 2021) Image caption: combination of treatments or other systemic treatments; white: other aspects of management; MDT, multidisciplinary team (Adopted from Crawford et al., 2021) Although this model has obvious advantages, it has also encountered some problems, such as heavy burden on caregivers, insufficient personalized care time, and an insufficiently humanized environment. Studies show that nurses in these environments are usually under more stress, and not all of them have received sufficient hospice care training, which may affect the quality of care. To improve this model, it is necessary to continuously carry out employee education, enhance collaboration in nursing, and change to more patient-centered and less invasive nursing practices when patients are approaching the final stage of life (Terzi and Kapucu, 2022; Jeong et al., 2023). 3.2 Family care and community Support models The home care and community support model focuses on providing end-of-life care in patients' homes or communities, with the aim of enabling patients to live comfortably in a familiar environment and maintain their quality of life. These models usually involve general practitioners, community nurses and family caregivers to
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