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. 3 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 Diagnostic Potential and Mechanisms of Tumor-Derived Exosomes in Liquid Biopsy Xiaopen Liu, Jie Zhang Cancer Genetics and Epigenetics, 2025, Vol. 13, No. 3, 106-116 Mechanisms and Therapeutic Strategies for Endocrine Resistance in Breast Cancer Xiaohong Yang, Liting Wang Cancer Genetics and Epigenetics, 2025, Vol. 13, No. 3, 117-125 Efficacy and Adverse Effects of Bevacizumab Combination Therapy in Advanced Colorectal Cancer Wei Zhang Cancer Genetics and Epigenetics, 2025, Vol. 13, No. 3, 126-135 Trends in CAR-T Cell Therapy for Hematologic Malignancies Qiyan Lou, Xiaoying Xu Cancer Genetics and Epigenetics, 2025, Vol. 13, No. 3, 136-144 Research Progress on Family-Involved Discharge Care Models for Cancer Patients Lipin Gao, Yanling He, Qiong Li, Yeli Huang Cancer Genetics and Epigenetics, 2025, Vol. 13, No. 3, 145-153
Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 106-116 http://medscipublisher.com/index.php/cge 106 Research Insights Open Access Diagnostic Potential and Mechanisms of Tumor-Derived Exosomes in Liquid Biopsy Xiaopen Liu, Jie Zhang Institute of Life Science, Jiyang College of Zhejiang A&F University, Zhuji, 311800, Zhengjiang, China Corresponding author: jie.zhang@jicat.org Cancer Genetics and Epigenetics, 2025, Vol.13, No.3 doi: 10.5376/cge.2025.13.0011 Received: 10 Mar., 2025 Accepted: 21 Apr., 2025 Published: 09 May, 2025 Copyright © 2025 Liu and Zhang, 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: Liu X.P., and Zhang J., 2025, Diagnostic potential and mechanisms of tumor-derived exosomes in liquid biopsy, Cancer Genetics and Epigenetics, 13(3): 106-116 (doi: 10.5376/cge.2025.13.0011) Abstract This study deeply analyzed the biological characteristics, mechanism of action and diagnostic advantages of TEXs in liquid biopsy, and simultaneously explored their influences in the processes of tumor deterioration, immune escape and the development of drug resistance, as well as their potential as biomarkers for the early detection, classification and real-time monitoring of cancer. Nowadays, new technologies for exosome separation and detection, such as microfluidics, biosensors, and analysis with the aid of artificial intelligence, are constantly emerging, which are driving their rapid development towards clinical applications. Although there are still difficulties in unifying standards and clinical promotion, TEXs is expected to promote the development of precision oncology and revolutionize the cancer diagnosis model with its minimally invasive detection technology. Keywords Tumor-derived exosomes; Liquid biopsy; Cancer biomarkers; Non-invasive diagnostics; Exosome technology 1 Introduction Liquid biopsy has rapidly become an important new method for cancer diagnosis. By analyzing biological body fluids such as blood, urine and saliva, it provides minimally invasive and timely tumor-derived substances. This technology can achieve early detection, formulate treatment plans based on the condition, monitor residual lesions and recurrence, and solve many deficiencies of traditional tissue biopsy, such as invasiveness and inaccurate sampling. Driven by the potential to improve cancer detection, prognosis assessment and personalized treatment strategies for various malignant tumors, the clinical application of liquid biopsy is continuously expanding (Song et al., 2020;Breakefield et al., 2021; Valencia and Montuenga, 2021; Cai et al., 2022; Jiang et al., 2022). Exosomes are a type of extracellular vesicles, ranging in size from 30 to 150 nanometers. Almost all cell types, including tumor cells, secrete exosomes, and they are abundant in body fluids. These nanovesicles contain a variety of biomolecules-DNA, RNA, proteins, lipids and metabolites-reflecting the molecular characteristics of the cells from which they originate. Because exosomes have a lipid bilayer structure, they are very stable in circulation, making them reliable carriers of tumor-specific information. Exosomes can reflect the genetic and signaling changes of tumor cells. Combined with their roles in intercellular information transmission and participation in the process of cancer development, they become highly potential biomarkers in liquid biopsy. Furthermore, compared with other circulating biomarkers (such as cell-free DNA and circulating tumor cells), they have obvious advantages in terms of stability, richness and multi-component analysis ability (Qin et al., 2018; Fitts et al., 2019; Song et al., 2020; Breakefield et al., 2021; Valencia and Montuenga, 2021; Cai et al., 2022). This study will comprehensively analyze the diagnostic potential of tumor-derived exosomes and the underlying mechanisms in the context of liquid biopsy. By integrating the latest developments in exosome isolation, molecular analysis and detection techniques, this article will focus on how exosomes can be applied in early cancer detection, disease monitoring and prognosis assessment. This article will also discuss the biological roles of exosomes in tumor progression and intercellular communication, as well as the challenges and future development directions faced in applying exosome-based liquid biopsy to clinical practice.
Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 106-116 http://medscipublisher.com/index.php/cge 107 2 Biological Characteristics of Exosomes 2.1 The origin, biogenesis and structural composition of exosomes Exosomes belong to nanoscale extracellular vesicles, with diameters typically ranging from 30 to 200 nanometers, and originate from endosomal chambers within cells. Its formation process is that the endosomal membrane indented inward to form polycystic vesicles (MVBs), which contain various cellular substances. When MVBs fuse with the cell membrane, exosomes will be released outside the cell (Edalat et al., 2020; LeBleu and Kalluri, 2020; Feng and Krylova, 2023). This process is strictly regulated and includes steps such as substance sorting, MVBs maturation, and membrane fusion, ultimately generating exosome populations with different molecular compositions (Kim et al., 2021; Yang et al., 2022). Structurally, exosomes are wrapped by a lipid bilayer membrane and contain a large amount of proteins, lipids, nucleic acids (DNA, mRNA, miRNA, lncRNA), and metabolites. These components can reflect the cellular origin of exosomes and whether the cells that produce them are in a normal or diseased state. The key components in exosomes include quad-transmembrane proteins (CD9, CD63, CD81), heat shock proteins and various signaling molecules, which make the structure of exosomes stable and their functions diverse (Qasim et al., 2019; LeBleu and Kalluri, 2020; Ayala-Mar et al., 2021; Dong et al., 2023). The special molecular characteristics of exosomes make them promising as markers for disease diagnosis and carriers for treatment. 2.2 Stability and transmembrane transport characteristics of exosomes Exosomes are very stable in biological body fluids, which is attributed to their lipid bilayer structure. It can protect the substances carried by exosomes from being decomposed by enzymes and is not afraid of harsh extracellular environments. This stability enables exosomes to circulate for a long time in body fluids such as blood, making them highly suitable for liquid biopsy and drug transport (Qasim et al., 2019; LeBleu and Kalluri, 2020). Moreover, exosomes have good compatibility with the human body and are less likely to trigger immune responses, thus having more advantages in clinical applications (Dong et al., 2023; Chen, 2024). Exosomes can cross biological barriers and transport the substances they carry to nearby or distant cells. It can be selectively absorbed by target cells through methods such as endocytosis, membrane fusion, or binding to receptors, thereby transferring bioactive molecules there (Edalat et al., 2020; Gurung et al., 2021; Ayala-Mar et al., 2021; Feng and Krylova, 2023). This precise transportation ability plays a key role in the transmission of information and regulation of cell functions by exosomes between cells. 2.3 The role of exosomes in intercellular communication and signal transduction Exosomes are important media for information transmission between cells. They can transport proteins, lipids and nucleic acids, and regulate various processes of the body's normal operation and illness. By transmitting these molecules, exosomes can alter the gene expression and signal transduction pathways of other cells, influencing immune responses, tumor development, tissue repair, etc. (Kourembanas, 2015; Qasim et al., 2019; Edalat et al., 2020; LeBleu and Kalluri, 2020; Kim et al., 2021; Dong et al., 2023). This ability to change the state of cells is the root cause of the significance of exosomes in the research of diseases such as cancer. During the process of cellular signal transduction, different substances carried by exosomes can activate or inhibit specific signal transduction processes in the target cells. For instance, exosomes produced by tumors may carry oncogenes, oncoproteins, or signal proteins that help tumors grow, metastasize, and evade the immune system (LeBleu and Kalluri, 2020; Yang et al., 2022; Dong et al., 2023). On the other hand, exosomes can also deliver therapeutic molecules or substances that regulate the immune system, which indicates that they can play a dual role in the development and treatment of diseases. The process by which exosomes transmit signals is complex and can be affected by the environment. It is precisely for this reason that they have great potential in disease diagnosis and treatment. 3 The Functional Roles of Tumor-Derived Exosomes 3.1 Promote the proliferation, invasion and metastasis of tumor cells Tumor-derived exosomes (TEXs) play a crucial role in the process of tumor deterioration, promoting the
Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 106-116 http://medscipublisher.com/index.php/cge 108 continuous growth of tumor cells, their invasion of surrounding tissues and metastasis. They can change the environment around the tumor, facilitate the formation of new blood vessels, and trigger epithelial-mesenchymal transition (EMT), all of which are important steps in tumor metastasis. TEXs can also promote the formation of the pre-metastatic microenvironment and make tumor cells more likely to invade and take root in distant tissues by delivering carcinogenic proteins and RNA to other cells (Zhang et al., 2018; Yousefi et al., 2019; Sun et al., 2021; Alavizadeh et al., 2022; Gao et al., 2025). These exosomes can alter the states of other cells, such as stromal cells and immune cells, creating an environment conducive to tumor growth. TEXs can adjust the permeability of blood vessels, weaken the immune system's monitoring of tumors, enable tumor cells to survive in the blood, and form new tumors. Some molecules in TEXs, such as specific micrornas and proteins, are directly involved in these processes, making them key factors in cancer metastasis (Zhang et al., 2018; Yousefi et al., 2019; Sun et al., 2021; Wang et al., 2022; Gao et al., 2025). 3.2 Participate in immune evasion and drug resistance mechanisms TEXs play a significant role in helping tumors evade attacks from the immune system. They can regulate the activity of various immune cells around the tumors. It can inhibit the functions of T cells, natural killer cells (NK), and dendritic cells, promote the increase of regulatory T cells and myeloid-derived suppressor cells, thereby forming an environment that enables tumor cells to evade immune examinations (Alavizadeh et al., 2022; Sarmadian et al., 2024; Gao et al., 2025). The hypoxic environment can make the immunosuppressive effect of TEXs stronger and better inhibit the anti-tumor response of immune cells (Yin et al., 2022). In addition to affecting immune function, TEXs is also associated with tumor drug resistance. They transfer molecules related to drug resistance, such as specific micrornas and proteins, to tumor cells that were originally sensitive to drugs, causing these cells to develop drug resistance. TEXs can also isolate therapeutic drugs or change the targets of drug action, reduce the efficacy of anti-cancer treatment, and lead to tumor recurrence and further deterioration (Zhang et al., 2018; Yousefi et al., 2019; Alavizadeh et al., 2022; Gao et al., 2025). 3.3 Specific molecular carriers reflecting the state of the tumor TEXs encapsulate a variety of biomolecules, including micrornas (miRNAs), long non-coding Rnas (lncRNAs), and proteins. These molecules can reflect the characteristics of the tumor cells from which they originate. These molecules transmit information between cells and are involved in regulating the gene expression, signal transduction processes and cellular activities of other cells (Zhang et al., 2018; Alavizadeh et al., 2022; Gao et al., 2025). For instance, micrornas in exosomes can prevent certain genes from being expressed. Long non-coding Rnas can adsorb micrornas or regulate gene transcription, thereby influencing the growth and metastasis of tumors (Wang et al., 2022; Zhang et al., 2022). These molecules in TEXs not only have important functions, but also can serve as biomarkers for cancer diagnosis and prognosis determination. The presence and content of specific micrornas, long non-coding Rnas and proteins in TEXs can reflect the type, development stage and therapeutic effect of tumors, which enables them to be applied in liquid biopsy to achieve non-invasive cancer monitoring and personalized treatment (Alavizadeh et al., 2022; Wang et al., 2022; Zhang et al., 2022; Gao et al., 2025). 4 The Diagnostic Potential of Exosomes in Liquid Biopsy 4.1 Stable exosomes are present in various body fluids suitable for non-invasive sampling Exosomes are abundantly present in various body fluids such as blood, urine, saliva and breast milk, which enables people to conveniently obtain them through non-invasive means for liquid biopsy (Jafarbeik-Iravani et al., 2017; Song et al., 2020; Cai et al., 2022). The lipid bilayer structure of exosomes is very stable, which can protect the molecules inside from being decomposed by enzymes and is not afraid of the harsh extracellular environment. In this way, during the collection and processing, the information used for diagnosis can remain complete (Qin et al., 2018; Breakefield et al., 2021; Wang et al., 2025).
Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 106-116 http://medscipublisher.com/index.php/cge 109 The stability and wide presence of exosomes make them reliable carriers of tumor markers. People can conduct cancer detection and disease monitoring through minimally invasive and multiple sampling methods (Breakefield et al., 2021). Compared with traditional tissue biopsy, isolating exosomes from easily accessible body fluids is more convenient for application in daily clinical work and can also make patients more comfortable (Jafarbeik-Iravani et al., 2017; Song et al., 2020; Cai et al., 2022; Wang et al., 2025). 4.2 The value of exosome biomarkers in the early detection and classification of cancers Biomarkers such as proteins, micrornas and other nucleic acids in exosomes have high diagnostic value in the early detection and type differentiation of various cancers such as lung cancer, breast cancer and pancreatic cancer (Zhu et al., 2020; Tusubira et al., 2022; Wang et al., 2025). For instance, through the micrornas and proteins in exosomes, cancer patients and healthy individuals can be distinguished, and the type and stage of tumors can also be determined, which is conducive to early treatment and the formulation of personalized plans (Jafarbeik-Iravani et al., 2017; Qin et al., 2018; Kang et al., 2020; Tusubira et al., 2022). When diagnosing pancreatic cancer, compared with other methods, liquid biopsy based on exosomes is more sensitive (0.93), has higher specificity (0.92), and the area under the curve (AUC) reaches 0.98, with very outstanding diagnostic accuracy (Zhu et al., 2020). Similarly, in the diagnosis of lung cancer and breast cancer, exosome markers can also achieve early detection and classification. Combined with deep learning and advanced spectroscopy techniques, the diagnostic effect will be better (Jafarbeik-Iravani et al., 2017; Qin et al., 2018; Kang et al., 2020). 4.3 Advantages over traditional tissue biopsy in terms of sensitivity and real-time monitoring Compared with traditional tissue biopsy, liquid biopsy based on exosomes has many obvious advantages. It is more sensitive in detecting tumor signals and can also grasp the tumor development and treatment effect in real time and dynamically (Jafarbeik-Iravani et al., 2017; Song et al., 2020; Kang et al., 2020; Breakefield et al., 2021; Tusubira et al., 2022). Tissue biopsy is not only invasive but also limited by tumor differences and inaccurate sampling. However, exosome analysis can reflect the tumor situation more comprehensively from multiple sites and stages (Figure 1) (Cai et al., 2022; Wang et al., 2025). Figure 1 Exosomal biomarkers of systemic tumors, application in tumors of different systems and some examples of biomarkers (Adopted from Wang et al., 2025)
Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 106-116 http://medscipublisher.com/index.php/cge 110 In addition, exosome sampling is non-invasive and convenient for multiple monitoring. Doctors can thereby track the changes in the condition, discover residual lesions, and evaluate the treatment effect in a timely manner (Kang et al., 2020; Breakefield et al., 2021; Tusubira et al., 2022). This ability of dynamic monitoring is conducive to formulating more personalized and flexible cancer treatment plans, which is expected to improve the prognosis of patients and reduce unnecessary invasive surgeries (Jafarbeik-Iravani et al., 2017; Song et al., 2020; Cai et al., 2022; Wang et al., 2025). 5 Advances in Exosome Analysis Technology 5.1 Separation techniques: supercentrifugation, nanomaterials, immunoaffinity method Supercentrifugation remains a commonly used method for separating exosomes. It relies on the centrifugal force generated by high-speed rotation to separate exosomes based on their size and density. Although supercentrifugation can better maintain the morphology of exosomes, the operation takes a long time, requires a large sample size, and impurities are prone to mix in during separation, resulting in the aggregation of exosomes and reducing purity (Hsu et al., 2019; Gopal et al., 2021). Precipitation-based methods such as total exosome separation reagents can separate more and purer exosomes, but they may also introduce non-exosome particles. Therefore, they should be carefully selected based on subsequent uses when in use (Burgy et al., 2020; Kumar et al., 2025). Nowadays, new technologies based on nanomaterials and the principle of immunoaffinity can be used to separate exosomes more precisely and efficiently. Microfluidic devices based on nanomaterials, along with aptamer capture technology, feature fast separation speed, high yield, good purity, and can also reduce sample usage and operation time (Demirci et al., 2021; Du et al., 2022). The immunoaffinity method separates exosome surface markers through antibodies or aptamers, but it has the problems of high cost and difficulty in large-scale application. The combination of these advanced methods is promoting the development of exosome isolation technology in clinical practice and research (Hsu et al., 2019; Shen et al., 2023; Hu and Gao, 2025). 5.2 Detection methods: qPCR, NGS, nanosensors, single-molecule analysis Quantitative PCR (qPCR) and next-generation sequencing (NGS) are important methods for detecting nucleic acids in exosomes, which can accurately detect and analyze genetic materials such as micrornas and messenger Rnas in exosomes These methods are highly specific and crucial for discovering disease-related biomarkers, but the prerequisite is to have a reliable exosome isolation and nucleic acid extraction process to ensure the accuracy of the results (Gopal et al., 2021; Yang et al., 2024). New achievements in nanosensor technology and single-molecule analysis have enhanced the ability to detect exosomes. Fluorescence sensors, electrochemical sensors, surface-enhanced Raman scattering (SERS) technology, and microfluidic-based biosensors, etc., can rapidly and sensitively detect proteins and nucleic acids in exosomes without labeling (Figure 2) (Demirci et al., 2021; Hu and Gao, 2025). These techniques can also be combined with signal amplification methods such as hybrid chain reaction or rolling loop amplification to improve detection accuracy and facilitate rapid diagnosis (Huang et al., 2021; Yang et al., 2024). 5.3 Technical challenges and standardization requirements: purity, sensitivity, repeatability Although exosome analysis technology has made significant progress, it still faces many challenges, especially in terms of the purity, sensitivity and repeatability of results in separation and detection. When isolating exosomes by traditional methods, impurities such as protein aggregates and lipoproteins are prone to be mixed in, which brings difficulties to subsequent analysis and the discovery of biomarkers (Burgy et al., 2020; Huang et al., 2021). Moreover, the methods for isolating exosomes in various laboratories are not uniform and there is a lack of standard procedures, resulting in inconsistent experimental results and hindering the transformation of related technologies into clinical applications (Hsu et al., 2019; Gopal et al., 2021; Du et al., 2022). There is an urgent need to formulate standard and reliable operation procedures now to ensure the high purity, high sensitivity and result repeatability of exosome analysis. The development of a new platform integrating microfluidics and biosensors, while unifying the norms of sample processing and data analysis, is crucial for
Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 106-116 http://medscipublisher.com/index.php/cge 111 promoting the development of exoexo-based diagnostic technologies and achieving reliable comparisons of different research results (Demirci et al., 2021; Huang et al., 2021; Du et al., 2022; Shen et al., 2023; Hu and Gao, 2025). Solving these problems will contribute to the wide application of exosome liquid biopsy technology in clinical practice. Figure 2 Schematic diagrams of microfluidic SERS-based aptasensors (Adopted from Hu and Gao, 2025) 6 Clinical Translation and Challenges 6.1 The current development status and clinical trial status of liquid biopsy products based on exosomes Liquid biopsy based on exosomes has rapidly moved from laboratory research to the clinical application stage. Currently, a variety of related products and detection methods are being evaluated or put into use in clinical Settings. It is particularly worth mentioning that the prostate cancer detection method based on exosome RNA has been used by tens of thousands of patients and incorporated into the clinical guidelines for early detection, which fully demonstrates the value of exosome diagnosis in practical applications (Breakefield et al., 2021). Clinical trials and studies have also shown that exobody-based diagnostic methods have achieved good results in the early detection, classification and disease monitoring of various cancers such as lung cancer, breast cancer, pancreatic cancer and sarcoma. Relevant personnel are committed to verifying their effectiveness in a larger patient population (Song et al., 2020; Caruso et al., 2023; Wang et al., 2025). Despite these advancements, most exosome-based liquid biopsy methods are still in the early stages of clinical transformation, and many applications are still in the clinical trial stage. At present, most exosome-based diagnostic methods are testing their capabilities in improving early diagnosis, predicting prognosis and monitoring
Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 106-116 http://medscipublisher.com/index.php/cge 112 treatment effects. However, to achieve wide clinical application, further verification and approval from regulatory authorities are still needed (Song et al., 2020; Caruso et al., 2023; Wang et al., 2025). Continuous research and large-scale clinical trials are crucial for determining the clinical value and reliability of exosome-based liquid biopsy products. 6.2 Issues in clinical application: standardization, ethical considerations and regulatory policies One of the major difficulties in the clinical application of liquid biopsy of exosomes is the lack of unified norms for the separation, identification and analysis of exosomes. Due to the different methods of sample collection, processing and analysis, inconsistent test results are prone to occur, and it is difficult to obtain the same or comparable results among different research and clinical institutions (Genova et al., 2019). Therefore, formulating unified operation methods and strict quality control measures is crucial for ensuring the reliability of exosome diagnostic results and their practical application in clinical practice (Breakefield et al., 2021; Cai et al., 2022; Wang et al., 2025). In the process of applying exosome liquid biopsy to clinical practice, ethics and supervision are also very important. As exosome testing is increasingly used in daily medical care, issues such as patient consent to participate in the testing, personal data protection, and how to handle unexpected test results must be properly addressed (Zhang et al., 2024). Before approving new diagnostic products, regulatory authorities need to have sufficient evidence to prove that the products are safe, effective and helpful for clinical treatment. This requires conducting well-planned clinical trials and reporting the trial results truthfully and clearly (Wang et al., 2025). 6.3 Obstacles and strategies for transforming research results into clinical practice The main obstacles faced in clinical transformation include: the technical difficulties in achieving high-purity and high-sensitivity exosome isolation, as well as the demand for an economical, scalable and easy-to-operate platform suitable for clinical laboratories (Breakefield et al., 2021). The biological characteristics of exosomes vary greatly and there is a lack of recognized biomarkers, which further increases the difficulty of developing standardized diagnostic methods (Cai et al., 2022; Jiang et al., 2022). Furthermore, there are no clear judgment criteria and reference ranges for exosome biomarkers, which also hinders their interpretation and application in clinical practice (Genova et al., 2019; Wang et al., 2025). To overcome these obstacles, cooperation among clinicians, researchers and enterprises is highly necessary. The strategies that can be adopted include: developing a new platform integrating microfluidic and biosensor technologies, conducting multi-center validation studies, and establishing a large and well-annotated biobank for the discovery and validation of biomarkers (Song et al., 2020; Cai et al., 2022). The active participation of regulatory authorities and the clarification of clinical application value through prospective trials are crucial for the successful application of exosome-based liquid biopsy in conventional cancer treatment (Breakefield et al., 2021; Jiang et al., 2022; Wang et al., 2025). 7 Future Development Directions 7.1 Integrate multimodal diagnosis and AI-assisted data analysis Combining exosome detection with other liquid biopsy methods, such as circulating tumor DNA (ctDNA), holds great promise for making the diagnostic results more accurate and comprehensive. Integrating multiple biomarker sources can present the molecular characteristics of tumors more completely, which is helpful for the early detection, type determination and disease monitoring of cancer. This multimodal diagnostic approach gives full play to the strengths of each biomarker and may overcome the shortcomings of single-biomarker detection to form a more reliable, sensitive and accurate cancer detection scheme (Kalluri and LeBleu, 2020). Artificial intelligence (AI) and machine learning are increasingly being applied in handling the complex data generated from exosome diagnosis. AI algorithms can efficiently analyze the spectral and image data collected by advanced biosensors, identify subtle patterns, and construct predictive models for precise diagnosis. The use of interpretable and uninterpretable AI models can enhance the transparency and accuracy of exosome diagnosis, laying the foundation for the application of real-time bedside diagnosis and mobile healthcare (Zhu et al., 2024).
Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 106-116 http://medscipublisher.com/index.php/cge 113 7.2 The potential of exosomes in individualized medicine and treatment response prediction Exosomes contain a variety of biomolecules and can reflect the changes of tumor cells, thus having great application value in personalized medicine. By analyzing the molecules in exosomes, doctors can understand the uniqueness of each patient's tumor, track the disease progression, and then formulate individualized treatment plans (Contreras-Naranjo et al., 2017). This personalized treatment method is expected to improve the therapeutic effect, reduce adverse reactions, and flexibly adjust the treatment strategy based on the immediate molecular detection results (Zhong et al., 2020; Tan et al., 2025). In addition, exosomes can serve as biological indicators for evaluating therapeutic effects, assisting doctors in determining which patients may benefit from specific treatments and which may develop drug resistance. Since exosomes can continuously reflect the tumor status in a non-invasive way, it is convenient for long-term monitoring of the disease and early intervention, which plays a key role in optimizing personalized cancer treatment (Zhong et al., 2020; Tan et al., 2025). 7.3 Establish a unified database and bioinformatics platform for research integration The research on exosomes has developed rapidly, generating massive amounts of data. Therefore, it is extremely urgent to build a unified database and an advanced bioinformatics platform. Centralized data storage centers can promote data sharing, unify research standards, conduct comprehensive analyses, and accelerate the speed of discovering and validating biomarkers in different patient groups and various types of cancers. These platforms are of great significance for summarizing research results, standardizing research methods and promoting cooperation within the field (Chen et al., 2022). Bioinformatics tools developed for exosome data can integrate multi-omics data, facilitate the construction of predictive models, and also enable comparative analysis among different studies. The establishment of these resources plays an important role in applying the research results of exosomes to clinical practice, ensuring the reproducibility of research results, and promoting the innovation of cancer diagnosis and treatment (Chen et al., 2022). 8 Concluding Remarks Exosomes have shown great clinical application potential in the field of liquid biopsy diagnosis of cancer. This is attributed to their stable nature in biological body fluids, the ability to carry various molecules, and the ability to reflect the molecular state of the source tumor cells. Exosomes are present in common body fluids such as blood, urine and saliva. By taking advantage of this characteristic, people can monitor tumor changes in real time through non-invasive methods, achieve early diagnosis and evaluate treatment effects, which has significant advantages over traditional tissue biopsy. Clinical research and trials have confirmed the role of exosome biomarkers in the diagnosis of various cancers. Detection methods based on exosome RNA have now been included in the clinical guidelines for the early detection of prostate cancer. To fully tap the potential of exosomes in diagnosis and prognosis determination, technological progress and biomarker discovery are indispensable. Recently, innovations in microfluidic chips, nanomaterials, advanced biosensors, etc. in the separation, enrichment and detection of exosomes have enhanced the sensitivity and accuracy of detection. Continuous research on molecular characteristics such as micrornas and proteins in exosomes can help discover more clinically available biomarkers. The combination with artificial intelligence and the adoption of multimodal diagnostic methods will further enhance diagnostic accuracy and promote the development of personalized medicine. The key to promoting the development of exosome liquid biopsy technology lies in opening up the pathway between basic research and clinical application. At present, there are still many challenges, such as the need to formulate unified operation norms, carry out large-scale clinical validation, and clarify regulatory procedures, so as to ensure the reliability and reproducibility of test results in clinical applications. The collaboration of all parties to establish a unified database, share research data and standardize research methods will accelerate the process of exosome liquid biopsy technology moving from the laboratory to the clinical field, ultimately facilitating the diagnosis of cancer, disease monitoring and improving the treatment effect of patients.
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Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 117-125 http://medscipublisher.com/index.php/cge 117 Research Insights Open Access Mechanisms and Therapeutic Strategies for Endocrine Resistance in Breast Cancer Xiaohong Yang, Liting Wang Hainan Institute of Biotechnology, Haikou, 570206, Hainan, China Corresponding author: liting.wang@hibio.org Cancer Genetics and Epigenetics, 2025, Vol.13, No.3 doi: 10.5376/cge.2025.13.0012 Received: 21 Mar., 2025 Accepted: 29 Apr., 2025 Published: 13 May, 2025 Copyright © 2025 Yang and 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: Yang X.H., and Wang L.T., 2025, Mechanisms and therapeutic strategies for endocrine resistance in breast cancer, Cancer Genetics and Epigenetics, 13(3): 117-125 (doi: 10.5376/cge.2025.13.0012) Abstract This study conducts a detailed analysis of the causes of endocrine resistance in breast cancer, such as abnormal estrogen receptor signaling, activation of signaling pathways like PI3K/AKT/mTOR, and changes in the surrounding environment of the tumor. This study also explored existing and emerging treatment approaches for drug resistance, such as the use of CDK4/6, PI3K and mTOR inhibitors, the development of second-generation serd and PROTACs drugs, and the formulation of personalized treatment plans by detecting biomarkers. In the future treatment of endocrine-resistant breast cancer, personalized treatment plans need to be adopted, the research results of multiple omics should be integrated, and collaborative research among different disciplines should be strengthened. Only in this way can new therapeutic targets be found and more appropriate treatments be provided for patients. Keywords Endocrine resistance; Estrogen receptor-positive breast cancer; Targeted therapy; PI3K/AKT/mTOR pathway; Precision medicine 1 Introduction Breast cancer is the most common cancer among women worldwide. Among them, cases of estrogen receptor-positive (ER+) breast cancer account for approximately 70%~80% of all breast cancer patients (Hanker et al., 2020; Nicolini et al., 2025). Breast cancer of type ER+is very important because it is usually sensitive to hormone-related treatment methods. Through this type of treatment, the recurrence rate and mortality rate of cancer in patients can be significantly reduced, and the treatment effect can be improved. However, even if the treatment is effective at the beginning, many ER+breast cancer patients will eventually develop resistance to endocrine therapy, which brings great difficulties to clinical treatment (Murphy and Dickler, 2016; Hanker et al., 2020; Sahin et al., 2021; Nicolini et al., 2025). Whether it is early or advanced ER+breast cancer, endocrine therapy is the main treatment approach (Ramaswamy and Zhao, 2014). Commonly used drugs include selective estrogen receptor modulators (SERMs), such as tamoxifen, aromatase inhibitors (AIs), and selective estrogen receptor degraders (SERDs), such as fulvestine (Perrone et al., 2005; Fan et al., 2015). These drugs work by inhibiting estrogen, which is crucial for the growth and survival of ER+breast cancer cells (Hanker et al., 2020; Sahin et al., 2021; Nicolini et al., 2025). After the advent of these drugs, the time without disease progression and the overall survival time of patients with hormone receptor-positive breast cancer were significantly prolonged. However, some patients have no response to treatment at the beginning, and some patients develop drug resistance after a period of treatment. This remains a major problem for long-term disease control (Murphy and Dickler, 2016; Hartkopf et al., 2020). This study will conduct an in-depth analysis of the causes of endocrine resistance in estrogen receptor-positive breast cancer and sort out the current and emerging treatment methods, with the aim of solving the problem of drug resistance. This study will also summarize the new findings of drug resistance-related research, evaluate the therapeutic effect of new combination therapies, and hope to find better treatment plans for patients with endocrine-resistant breast cancer and improve treatment outcomes.
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