Investigational New Drugs最新文献

{"title":"Pharmacokinetics, efficacy and safety of palbociclib and fulvestrant in a patient with hormone receptor-positive, human epidermal growth factor receptor 2 negative metastatic breast cancer with end-stage renal disease undergoing hemodialysis: A case report.","authors":"Toshiaki Takakura, Tsutomu Iwasa, Chiyo K Imamura, Satomi Watanabe, Hidetoshi Hayashi","doi":"10.1007/s10637-025-01564-1","DOIUrl":"https://doi.org/10.1007/s10637-025-01564-1","url":null,"abstract":"<p><p>Palbociclib combined with fulvestrant is a standard treatment for hormone receptor-positive, human epidermal growth factor receptor 2 (HER2) -negative metastatic breast cancer. Both agents are mainly eliminated by hepatic metabolism, and it is recognized that no dose adjustment is required for patients with renal impairment according to their prescribing information. However, their pharmacokinetics in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) were not studied in their development phases. We here report a case of 62-year-old female with ESRD on HD who was treated with palbociclib and fulvestrant. Palbociclib was initiated at a reduced dose of 100 mg/day (standard dose of 125 mg/day) and fulvestrant at a standard dose of 500 mg/body for multiple metastases. Along with dose adjustment of palbociclib due to hematologic toxicities, stable disease (SD) was maintained for 18 months. We also assessed the pharmacokinetics of palbociclib and fulvestrant at the first dose with HD and at steady state. Although the starting dose of palbociclib was reduced, the area under the concentration-time curve from 0 to 24 h (AUC_0-24) and the maximum concentration (C_max) at steady state were higher than those observed in patients with normal renal function receiving 125 mg/day in a Phase I study. Plasma concentrations of fulvestrant at steady state were almost within the range from the mean minimum concentration (C_min) to the mean C_max in patients receiving 500 mg/body in a Phase II study. This report suggests that palbociclib and fulvestrant combination therapy is manageable and effective in patients with ESRD.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical features, treatment and outcomes of dabrafenib-associated uveitis.","authors":"Jieqiong Liu, Wei Sun, Chunjiang Wang","doi":"10.1007/s10637-025-01569-w","DOIUrl":"https://doi.org/10.1007/s10637-025-01569-w","url":null,"abstract":"<p><strong>Background: </strong>To explore the clinical characteristics of dabrafenib-associated uveitis and provide a basis for diagnosis and treatment.</p><p><strong>Methods: </strong>The database was retrieved to collect reports of dabrafenib-associated uveitis and clinical data were collected for retrospective analysis.</p><p><strong>Results: </strong>Twenty-six patients were included in the study, with a median age of 56 years (range 30, 75). The onset time of uveitis was 3 months (range 0.75, 96) after administration. The types of uveitis were pan-uveitis (38.5%), anterior uveitis (34.6%), posterior uveitis (15.4%), and intermediate uveitis (3.8%). Fifty percent of the patients were Vogt-Koyanagi-Harada disease-like uveitis. After discontinuation of dabrafenib and treatment with topical and systemic steroids, the symptoms of uveitis improved in all patients.</p><p><strong>Conclusion: </strong>Patients are advised to have regular ophthalmology examinations during the use of dabrafenib. Timely administration of systemic or local corticosteroid treatment can significantly improve the symptoms of patients.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of engineered-exosome delivered si-HER2 and trastuzumab in the treatment of HER2-positive gastric cancer.","authors":"Yuehong Zhu, Yaoyang Guo, Ziyi Dong, Mingqing Zhang, Hui Liu, Xinyi Wen, Wenwen Pang, Xipeng Zhang, Zhansheng Jiang, Chong Chen, Jie Hao, Ming Gao, Haiyang Zhang","doi":"10.1007/s10637-025-01558-z","DOIUrl":"https://doi.org/10.1007/s10637-025-01558-z","url":null,"abstract":"<p><p>Trastuzumab is currently a key targeted drug for HER2-positive gastric cancer (GC), but there are common problems of drug resistance and cardiotoxicity in clinical treatment, resulting in poor therapeutic effects. Exosomes are natural nanocarriers for drug delivery and engineered exosomes have been widely used in translational medicine research. This study is designed to compare the anti-tumor effects and adverse effects between engineered exosomes carrying HER2 siRNA and trastuzumab. The stable cell line of iRGD-293T was constructed by using lentiviruses, and iRGD-293T and 293T cells were transfected with si-HER2 and exosomes were isolated by ultra-centrifugation. Functional experiments were performed to examine the inhibitory effects of iRGD-exo-si-HER2 and trastuzumab on both HER2-positive GC cells and mouse xenograft models. Blood biochemical indexes were used to test the adverse effects, especially cardiotoxicity. The engineered exosomes modified by iRGD peptide showed higher tumor affinity compared to control exosomes in vitro and in vivo. si-HER2 delivered by iRGD-exosomes significantly inhibited the proliferation and promoted apoptosis of HER2-positive GC cells, and iRGD-exo-si-HER2 significantly reduced the expression of HER2 in GC cells in vitro and in vivo, showing similar efficacy as trastuzumab but with lower cardiac side effects. Our data indicated that iRGD-exo-si-HER2 shows good anti-tumor effect both in vivo and in vitro, and has fewer side effects compared with trastuzumab. And this study suggested that engineering exosomes with si-HER2 can serve as novel strategy for the treatment of HER2-positive GC.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and optimization of PLGA-based gemcitabine nanocapsule for enhanced pancreatic cancer efficacy.","authors":"Gaurav Tiwari, Satyajit Panda, A Salomy Monica Diyya, Noel Vinay Thomas, Trinayan Deka, Shashi Ravi Suman Rudrangi, Gaurav Patel, Pankaj Sharma","doi":"10.1007/s10637-025-01567-y","DOIUrl":"https://doi.org/10.1007/s10637-025-01567-y","url":null,"abstract":"<p><p>This study aimed to develop gemcitabine-loaded nanocapsules for pancreatic cancer treatment, optimizing their formulation before evaluating them through in vivo studies. The researchers selected gemcitabine as the model drug because it has established clinical relevance and known pharmacokinetic shortfalls (short half-life and poor bioavailability) with toxic dose limits which suit the evaluation of nanoparticle drug delivery systems. The researchers conducted a 3² factorial design to optimize the formulation through adjustments of PLGA concentration and Tween 80 concentration. The optimal characteristics of F5 among nine formulations included particles of 160 ± 3 nm with 87 ± 2% encapsulation efficiency and - 27.8 ± 1.2 mV zeta potential. The in vitro drug release testing alongside pharmacokinetic results established that nanoparticle gemcitabine caused extended drug delivery and dramatically better bioavailability in addition to achieving longer systemic circulation than free gemcitabine alone. Evaluation of biodistribution revealed that the product displayed tumor-targeting property and had improved antitumor effect and less side effect compared with the other groups. The findings demonstrate that gemcitabine works as an ideal model chemotherapy drug to measure nanocarrier delivery platforms for treating pancreatic cancer solid tumors.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing the drug development challenge for rare pediatric diseases in Japan: a case study of isotretinoin.","authors":"Shota Inoue, Akihiko Ozaki, Hayase Hakariya, Jungang Zhao, Ivan D Florez, Yoshihiko Morikawa, Tetsuya Tanimoto","doi":"10.1007/s10637-025-01566-z","DOIUrl":"https://doi.org/10.1007/s10637-025-01566-z","url":null,"abstract":"<p><p>Drug lag in rare pediatric diseases remains a significant challenge in Japan despite its sophisticated healthcare system. We examined this issue through a case study of isotretinoin, an established standard drug for high-risk neuroblastoma (affecting 45-60 new patients annually in Japan) since the 2000s that has not been granted regulatory approval in Japan as of 2025. Analysis of regulatory documents and clinical practices revealed that while isotretinoin has demonstrated improved event-free survival rates in international trials when used as maintenance therapy for high-risk neuroblastoma, multiple barriers have hindered its domestic approval. These include the challenges of conducting clinical trials in limited pediatric populations, substantial development costs, diminishing market attractiveness due to Japan's demographic shift, and restrictions on \"mixed billing system\" which means combining covered insurance treatments with uncovered treatments under the universal health insurance system in Japan. Currently, patients must rely on costly private imports or clinical trial participation to access the drug, leading to financial burdens and treatment discontinuation risks. Recent regulatory reforms, including the establishment of the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs in 2009 and amendments enabling investigator-led trials, have facilitated progress. An investigator-led Phase II clinical trial evaluating isotretinoin's safety and efficacy is ongoing since 2023, with expected completion in 2026. However, the lengthy timeline of approximately 25 years from global adoption to potential approval highlights persistent challenges in pediatric drug development and Japan's isolation from global drug development networks. This case demonstrates the need for innovative policy approaches to ensure sustainable drug development for rare pediatric diseases in an aging society.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-dose PD-1 inhibition in relapsed/refractory classic Hodgkin lymphoma: systematic review and meta-analysis.","authors":"Mobil Akhmedov, Pervin Zeynalova, Alexander Fedenko, Andrey Kaprin","doi":"10.1007/s10637-025-01565-0","DOIUrl":"https://doi.org/10.1007/s10637-025-01565-0","url":null,"abstract":"<p><strong>Introduction: </strong>No correlation between the dose, adverse events, and efficacy was detected in clinical trials of anti-PD-1 antibodies across a range of solid and hematological malignancies. Given that dose reduction with potentially comparable clinical efficacy may improve access to treatment, particularly in low-income regions, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of low-dose PD-1 inhibitor monotherapy in relapsed/refractory (r/r) classic Hodgkin lymphoma (cHL).</p><p><strong>Materials and methods: </strong>Relevant reports were identified through PUBMED, MEDLINE, Cochrane, ScienceDirect databases, and major international conference proceedings, from inception till December 1, 2024. The risk of bias was assessed independently by two authors using the Joanna Briggs's critical appraisal checklist for studies reporting prevalence data. Heterogeneity was assessed using Cochran's Q test, with statistical significance defined as p < 0.05; I² statistic was used to quantify heterogeneity. Random effects models (Der-Simonian method) was used to pool results from primary studies in the presence of significant heterogeneity.</p><p><strong>Results: </strong>After screening, 13 reports including 148 patients were included in the systematic review. After exclusion of duplicated reports, studies with less than 5 patients, and studies with unextractable data, five studies with a total of 84 patients were included in the meta-analysis. The pooled objective response rate (ORR) with low-dose PD-1 inhibition in r/r cHL, as determined by meta-analysis, was 87% (95% CI, 71.9%-100%), with a corresponding complete response (CR) rate of 53.9% (95% CI, 34.7%-73.1%). The ORR with low-dose nivolumab was 83.8% (95% CI, 64.2%-100%), with a CR rate of 43.3% (95% CI, 29.7%-56.9%). The pooled rate of any-grade adverse events after low-dose PD-1 inhibition was 55.7% (95% CI, 36.1%-75.3%), with a grade 3-4 adverse event rate of 7.5% (95% CI, 1.7%-13.3%).</p><p><strong>Conclusions: </strong>This systematic review and meta-analysis demonstrated the high efficacy and acceptable toxicity of low-dose PD-1 inhibition in r/r cHL.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and pharmacokinetics of FCN-437c, a novel cyclin-dependent kinase 4/6 inhibitor, in Chinese patients with hepatic impairment.","authors":"Jia Xu, Jingrui Liu, Yanhua Ding, Xiaoran Yang, Yunjie Fu, Yi Sun","doi":"10.1007/s10637-025-01552-5","DOIUrl":"https://doi.org/10.1007/s10637-025-01552-5","url":null,"abstract":"<p><p>This study explored the impact of hepatic impairment on the safety and pharmacokinetics (PK) of FCN-437c, a novel dual CDK4/6 inhibitor for potential breast cancer treatment. In an open-label trial, 25 subjects (8 with mild hepatic impairment, 8 with moderate hepatic impairment, and 8 healthy controls matched for age, sex, and body weight) received a single 200-mg dose of FCN-437c. Results showed that FCN-437c was generally well-tolerated, with no serious adverse events. In mild hepatic impairment group, total FCN-437c C_max increased by 9.5%, while AUC_0-t and AUC_0-∞ decreased by 4.8%. Free drug exposure increased by 24.7%, 8.4%, and 8.4%. In moderate hepatic impairment group, total FCN-437c C_max, AUC_0-t, and AUC_0-∞ decreased by 16.7%, 17.1%, and 15.7%, and free drug exposure increased by 47.8%, 47.0%, and 49.6%. Overall, no clinically relevant differences in FCN-437c exposure were found between subjects with mild or moderate hepatic impairment and normal controls, but moderate hepatic impairment increased free drug exposure. Thus, no dose adjustment is needed for patients with mild hepatic impairment, but a reduced dose may be necessary for those with moderate hepatic impairment. Trial Registration: www.clinicaltrials.gov identifier NCT06620731 (retrospectively registered).</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting neuroblastoma with hydroxamic acid based HDAC1 and HDAC2 inhibitors: Insights from in vitro and in vivo studies.","authors":"Padmini Pai, Yashaswini Reddy, Ipshita Das, Babu Santhi Venkidesh, Poonam Bhandari, Pallavi Rao, Srinivas Oruganti, Keshava Prasad, Manasa Gangadhar Shetty, Kapaettu Satyamoorthy, Babitha Kampa Sundara","doi":"10.1007/s10637-025-01559-y","DOIUrl":"https://doi.org/10.1007/s10637-025-01559-y","url":null,"abstract":"<p><p>Histone deacetylases (HDACs) serve a crucial function in transcription regulation, and their dysregulation is linked to numerous diseases, including cancer. Among them, HDAC1 and HDAC2 are particularly significant in neural progenitors and are frequently overexpressed in neural-derived cancers. HDAC inhibitors (HDACis) have shown promise in overcoming chemoresistance by restoring tumor suppressor function in neuroblastoma cells. However, the lack of selectivity in existing HDACis presents challenges, highlighting the need for isoform-selective inhibitors to reduce side effects. This research investigated the anticancer properties of a newly synthesized hydroxamic acid derivative, emphasizing its selective HDAC1 and HDAC2 inhibition and strong antitumor activity. Our findings demonstrated that the newly developed hydroxamic acid analogues, 3A and 3B, effectively inhibited neuroblastoma cells (SH-SY5Y) proliferation, with IC₅₀ values of 8.49 µM and 4.44 µM, respectively, comparable to suberoylanilide hydroxamic acid (SAHA) with IC₅₀ of 0.91 µM. Additionally, compounds 3A and 3B exhibited potent HDAC inhibition. Compound 3A selectively inhibited HDAC2 with an IC₅₀ value of 0.89 μM, while compound 3B showed dual inhibition of HDAC1 and HDAC2, with IC₅₀ values of 0.44 μM and 1.94 μM, respectively. Compound 3B triggered cell cycle arrest in the G2/M phase, reduced colony formation efficiency, and altered cellular architecture upon treatment, further highlighting its anticancer potential. In an in vivo xenograft model, compound 3B significantly decreased tumor growth and tumor weight, highlighting its potential as an effective anticancer agent for neuroblastoma, offering both isoform-selective HDAC inhibition and potent anticancer effects.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical presentation of PD-1/PD-L1 immune checkpoint inhibitors induced cystitis.","authors":"Jian Xiao, Shanting Tang, Zhi Xia, Yuxin Zhou, Min Fang","doi":"10.1007/s10637-025-01563-2","DOIUrl":"https://doi.org/10.1007/s10637-025-01563-2","url":null,"abstract":"<p><p>This study aims to systematically analyze the clinical features of cystitis induced by anti-PD-1/PD-L1 drugs, with a view to providing a basis for early warning, diagnosis, and standardized management of this adverse reaction in clinical practice. In this study, we comprehensively searched multiple databases to systematically collect all case reports involving cystitis induced by anti-PD-1/PD-L1 drugs from the initiation of relevant research up to May 20, 2025, and conducted an in-depth retrospective analysis of these cases. The clinical characteristics of 43 patients with cystitis induced by anti-PD-1/PD-L1 agents in this study showed a median age of 57 years (27-78 years), with 26 cases (60.5%) being male. The median time from the initiation of these agents to cystitis onset was 96 days (9-510 days). Diagnosis confirmed that 81.4% cases were non-infectious cystitis, and antibiotic treatment was often ineffective or showed suboptimal efficacy. After discontinuing the relevant drugs and administering appropriate steroids, patients generally had a favorable prognosis. Notably, reinitiating anti-PD-1/PD-L1 therapy was associated with a significantly increased risk of cystitis recurrence. Cystitis is a rare adverse reaction during PD-1/PD-L1 immune checkpoint inhibitor therapy, which can impact patients' quality of life. It is notable that nearly all cases can be effectively managed through timely intervention and standardized pharmacotherapy. Therefore, early identification of cystitis induced by these drugs and the implementation of appropriate management strategies are crucial for improving patient outcomes.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The therapeutic potential of exosomes in bone cancers: osteosarcoma, chondrosarcoma, and Ewing sarcoma.","authors":"Nawfal Yousif Jamil, Mohammed S Nawrooz, Ashok Kumar Bishoyi, Suhas Ballal, Abhayveer Singh, T Krithiga, Rajashree Panigrahi, Zarrina Babamuradova, Sada Ghalib Taher, Mariem Alwan, Mahmood Jawad, Hiba Mushtaq","doi":"10.1007/s10637-025-01551-6","DOIUrl":"https://doi.org/10.1007/s10637-025-01551-6","url":null,"abstract":"<p><p>Osteosarcoma (OS), chondrosarcoma (CHS), and Ewing sarcoma (EwS) are the most common primary bone cancers (BCs). Among primary malignant tumors of the bones, OS is the most common, mainly affecting young people (4.8 per 1,000,000). The treatment of bone cancer (BC) is challenging for current medicine owing to its substantial incidence and the vast heterogeneity of malignant lesions within bone tissue. Due to the limitations of current therapies, researchers developed new strategies to treat BC. Exosomes (EXOs) play a crucial role in the development, progression, metastasis, and drug delivery of BCs, such as OS, EwS, and CHS. Hierarchical translation via tissue-specific reactions and cell-specific molecular signaling pathways accounts for the various therapeutic effects of EXOs produced from stem cells. The aim of this review is to highlight the critical role of EXOs derived from multiple cells, such as mesenchymal stem cells, immune cells, and tumor cells, in BCs, including OS, CHS, and EwS. Additionally, we provide a concise overview of how tumor-derived EXOs induce BCs. To lessen the adverse effects of EXOs on patients with BC and to provide more effective and focused treatments, it is necessary to understand these pathways. Moreover, we reviewed the potential of using EXOs as drug delivery systems for the treatment of BCs. Finally, we discussed the pros and cons of this therapeutic approach for BCs.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}