Investigational New Drugs最新文献

{"title":"Correction to: Prostate cancer cells' growth is decreased by novel MYC inhibitors.","authors":"Bita Nickkholgh, Joseph McGrath, Sivanandane Sittadjody, Jay Chauhan, Kwan-Young Jung, Steven Fletcher, K C Balaji","doi":"10.1007/s10637-026-01620-4","DOIUrl":"10.1007/s10637-026-01620-4","url":null,"abstract":"","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251510","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":"Prostate cancer cells' growth is decreased by novel MYC inhibitors.","authors":"Bita Nickkholgh, Joseph McGrath, Sivanandane Sittadjody, Jay Chauhan, Kwan-Young Jung, Steven Fletcher, K C Balaji","doi":"10.1007/s10637-026-01613-3","DOIUrl":"10.1007/s10637-026-01613-3","url":null,"abstract":"<p><p>The MAX (MYC-associated protein X) was discovered as an obligate heterodimer of MYC, a protein product of a prolific proto-oncogene that is dysregulated in over three-fourths of cancers. Targeting MYC directly is fraught with challenges due to the disordered structure of the MYC protein that is not conducive for small molecule inhibitor design. Therefore, the MYC/MAX protein-protein interaction provides an opportunity for indirect targeting of MYC. We compared the efficacy of first- and second-generation MYC/MAX small molecular inhibitors, 10,058-F4 and 3jc48-3 respectively, and tested the novel class of proteomimetic MYC/MAX inhibitor JKY-2-169 on inhibiting growth of human prostate cancer cell line DU145 in 2D culture. In addition, we validated the efficacy of inhibitors using 3-dimensional (3D) systems: 3D microcapsules and human prostate cancer spheroids generated by harvesting fresh cancerous tissue from human radical prostatectomy surgical specimens. Treatment in both 3D models showed that 3jc48-3 and JKY-2-169 reduced cell viability. Analysis of patient-derived spheroids before and after treatment showed that spheroid growth increased significantly over time only in the DMSO control group, while inhibitor-treated spheroids did not show significant growth during the same period; among the treatment groups, only 3jc48-3 significantly reduced spheroid size compared with the DMSO control. The results suggest that the proteomimetic and second-generation MYC inhibitors suppress cell growth at lower concentrations compared to the first-generation inhibitors. Comparative proteomic analysis of treated and untreated DU145 cells, based on a pre-defined twofold expression threshold, identified common cellular pathways altered by MYC/MAX inhibition primarily involving cytoskeletal organizations, cell cycle regulation, metabolism, and RNA-related functions. This study provides promising preliminary in vitro support for further investigation and development of novel MYC inhibitors.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"243-252"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771587","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":"Hedgehog Inhibitor and Paclitaxel: A Phase I Trial of the Oral Hedgehog inhibitor Taladegib in Combination with Weekly Paclitaxel in Patients with Advanced Solid Tumours.","authors":"Rosalind Glasspool, Sarah Patricia Blagden, Michelle Lockley, Elaine McCartney, Carol Evans, Fiona Thomson, Jennifer Brown, Laura Spiers, Chantevy Pou, Liz-Anne Lewsley, Iain A McNeish, T R Jeffry Evans","doi":"10.1007/s10637-026-01612-4","DOIUrl":"10.1007/s10637-026-01612-4","url":null,"abstract":"<p><p>The hedgehog (Hh) signalling pathway is aberrantly activated in solid tumours. Inhibition of Hh signalling by SMO inhibitors is effective in the treatment of basal cell carcinomas and medulloblastomas whereas combination treatments may be required in other solid tumours. When given with an SMO inhibitor in preclinical models, the efficacy of paclitaxel is enhanced and there is potential reversal of mechanisms of resistance to paclitaxel supporting clinical investigation of the combination. In this phase I trial, the safety and feasibility of the oral SMO inhibitor, taladegib, was evaluated in combination with weekly paclitaxel in patients with advanced solid tumours. This was an open-label, nonrandomised, multicentre, dose escalation trial using a standard 3 + 3 design (EudraCT: 2014-004695-37 ISRCTN15903698). Primary objectives were to determine dose-limiting toxicities and the maximum tolerated dose of the combination. Patients received up to 6 cycles of paclitaxel 80 mg/m2 (day 1, 8 and 15 of a 28-day cycle). Then, 16 patients were recruited into 3 cohorts and received taladegib at 100 mg, 200 mg and 400 mg once daily, respectively. Grade 2/3 peripheral sensory neuropathy was the dose-limiting toxicity. The maximum tolerated dose of taladegib in combination with weekly paclitaxel was 200 mg once daily. Four patients had a partial response and 4 had confirmed stable disease at 16 weeks. The combination is feasible but cumulative neuropathy may limit longer term treatment. Hh signalling may be implicated in chemotherapy-induced neuropathy.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"264-273"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase I study of TRK-950, an Anti-CAPRIN-1 antibody, as monotherapy and in combination with nivolumab in Japanese patients with advanced solid tumors.","authors":"Takafumi Koyama, Kan Yonemori, Jun Sato, Yuki Katsuya, Mao Okada, Tatsuya Yoshida, Fumiyoshi Okano, Noboru Yamamoto","doi":"10.1007/s10637-026-01609-z","DOIUrl":"10.1007/s10637-026-01609-z","url":null,"abstract":"<p><p>CAPRIN-1 is a cytoplasmic phosphoprotein strongly expressed on the membrane surface of cancer cells in most solid tumors but not on normal cells. TRK-950 is a first-in-class humanized antibody that targets CAPRIN-1 and demonstrates antitumor effects via immune cell engagement. This phase I study assessed the tolerability and safety of TRK-950 in Japanese patients, both as monotherapy and in combination with nivolumab, and evaluated pharmacokinetic and exploratory efficacy. Part 1 involved TRK-950 monotherapy at 5 or 10 mg/kg weekly for patients with advanced solid tumors; Part 2 included combination therapy with TRK-950 (10 mg/kg weekly or 20 mg/kg biweekly) plus nivolumab (240 mg biweekly). The primary endpoints were safety and tolerability; the secondary endpoints were pharmacokinetics, immunogenicity, and exploratory antitumor activity. Thirteen patients were enrolled. No dose-limiting toxicity occurred. Adverse events (AEs) of any grade with a frequency ≥ 20% were, in Part 1, alanine aminotransferase increased, constipation, and nausea and, in Part 2, pyrexia. The incidence of AEs did not appear to be dose dependent. In Part 1, 1 patient with melanoma achieved a partial response, and the response was sustained for an extended period. In Part 2, no responses were observed. TRK-950, as monotherapy or combined with nivolumab, was safe and well tolerated in Japanese patients with observed antitumor activity. TRK-950 is currently being evaluated in ongoing clinical studies: phase II study in patients with melanoma (NCT05423262) and phase II study in patients with gastric cancer (NCT06038578).Trial registration ClinicalTrials.gov, NCT05423262.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"211-225"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Class-level DILI saturation and hERG-driven risk stratification among 2024-2025 FDA-approved kinase inhibitors: an in silico multi-platform safety analysis.","authors":"Nihan Küçük Yılmaz, Veysel Baskın","doi":"10.1007/s10637-026-01615-1","DOIUrl":"10.1007/s10637-026-01615-1","url":null,"abstract":"<p><p>Newly approved kinase inhibitors (2024-2025) have limited post-approval safety data. We developed a weighted ToxPi framework to prioritize multi-endpoint liabilities spanning hERG cardiotoxicity, DILI, Ames genotoxicity, and CYP3A4-mediated drug-drug interaction potential. Thirteen compounds (12 KIs approved in 2024-2025 plus imatinib as a historical reference anchor) were profiled using ADMETlab 3.0, vNN-ADMET, and SwissADME (formula inputs) and integrated into a weighted composite (wToxPi = 0.30 × hERG + 0.30 × DILI + 0.20 × Ames + 0.20 × CYP3A4). Robustness was assessed across weighting schemes and sensitivity analyses addressing fusion-recoding scenarios, CYP3A4 platform asymmetry, and combination-regimen confounding. DILI signal saturation dominated the cohort: 12 of 13 compounds showed DILIcon ≥ 0.80, limiting hepatic discrimination and shifting differentiation to hERG and Ames variability. Sevabertinib (0.860), Zongertinib (0.840), and Lazertinib (0.775) ranked highest, whereas Mirdametinib (0.080) was the structural outlier. Ranking remained stable: ADMETlab-only and thresholded majority-vote alternatives preserved the principal structure (Spearman ρ = 0.780 and 0.812), whereas soft-label pseudo-probability mapping showed near-identity concordance (ρ = 0.978); a broader sensitivity grid (p = 0.60-0.90) confirmed structural stability (ρ = 0.929-0.995). Exploratory FAERS findings provided supportive post-marketing context. This framework provides transparent, reproducible, hypothesis-generating prioritization of newly approved KIs. Class-level DILI saturation reinforces the need for close hepatic surveillance in pharmacovigilance interpretation regardless of composite rank; hERG and Ames provide the main inter-compound discriminatory signal. Sevabertinib, Zongertinib, and Lazertinib ranked highest, whereas Mirdametinib was the structural outlier; for Inavolisib and Tovorafenib, endpoint-specific hepatic surveillance remains warranted irrespective of composite rank. The model should support pharmacovigilance prioritization rather than replace clinical monitoring or individualized risk assessment.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"253-263"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pooled safety analysis of lurbinectedin plus irinotecan in patients with advanced solid tumors.","authors":"Alejandro Falcón, Gregory M Cote, Javier Molina-Cerrillo, Axel Le Cesne, Pedro Rocha, Bruno Bockorny, David Paez, Javier Martin-Broto, Sant P Chawla, Sara Martinez, Carmen Kahatt, Vicente Alfaro, Mariano Siguero, Javier Jimenez, Ana Custodio, Vicente Alonso-Orduña, Carlos López, Attila Kollár, Juan José Soto-Castillo, Luis Paz-Ares","doi":"10.1007/s10637-026-01616-0","DOIUrl":"10.1007/s10637-026-01616-0","url":null,"abstract":"<p><p>Lurbinectedin in combination with irinotecan showed synergistic antitumor activity in preclinical studies. A phase I/II trial (NCT02611024) evaluated this combination in patients with advanced solid tumors. The phase II stage evaluated the antitumor activity of the recommended dose (RD) (lurbinectedin 2.0 mg/m² on Day (D)1 plus irinotecan 75 mg/m² on D1 and D8 q3wk with primary granulocyte colony-stimulating factor prophylaxis) in five tumor-specific cohorts. This pooled analysis describes the safety profile of this combination from 233 patients with different advanced solid tumors treated at the RD. Adverse events (AEs) and laboratory abnormalities were graded using NCI-CTCAE v.4. The most frequent AEs (any grade) related to treatment were fatigue (71% of patients/25% of cycles), diarrhea (62%/17%), nausea (59%/18%), vomiting (35%/7%) and decreased appetite (32%/6%); the most common grade ≥ 3 AEs were fatigue (14%/2%), diarrhea (14%/2%) and febrile neutropenia (9%/1%). The most common grade ≥ 3 laboratory abnormality regardless of relationship was neutropenia (53%). The rate of discontinuation due to treatment-related AEs was 3% (n = 7 patients). There was one treatment-related death (0.4%) involving a 63-year-old male patient (0.4%) diagnosed with metastatic NEN who died due to grade 5 staphylococcal bacteremia. In conclusion, this pooled analysis shows a predictable and manageable safety profile for lurbinectedin in combination with irinotecan in patients with advanced solid tumors, with myelosuppression, fatigue and gastrointestinal disorders being the main toxicities observed.Trial code: ClinicalTrials.gov identifier: NCT02611024.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"274-283"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial blueprint of colorectal cancer identifies Hypoxic CAF program that orchestrates Go-or-Grow decisions and predicts outcomes.","authors":"Mingkai Chen, Juan Yang, Jin Wang, Guangrun Du, Lida Zhang","doi":"10.1007/s10637-026-01611-5","DOIUrl":"10.1007/s10637-026-01611-5","url":null,"abstract":"<p><p>The tumor microenvironment (TME) critically influences colorectal cancer (CRC) progression, but its spatial organization and functional impact remain incompletely understood. We integrated single-cell transcriptomics (412,208 cells) with spatial transcriptomics (76,627 spots from 38 sections of 32 patients) to deconstruct the CRC microenvironment, employing computational approaches for niche identification, SCENIC network inference, and cell-cell communication analysis. Key findings were validated in primary CAF cultures, Seahorse metabolic analysis, and the TCGA cohort. We identified nine microenvironmental niches, including a co-localized \"pro-tumorigenic triad\" (desmoplastic stromal, angiogenic inflammatory, and TAM-dominant suppressive niches), creating an integrated ecosystem supporting tumor growth. We discovered a Hypoxic CAF subtype associated with a spatial \"Go-or-Grow\" switch in tumor cells-proximity to Hypoxic CAFs inversely correlated with proliferation but positively with invasion and metabolic stress programs. HMGA2 was identified as a key transcriptional regulator of this CAF state, which was significantly associated with adverse clinical outcomes in univariate survival analysis. In vitro co-culture experiments showed that these CAFs suppress proliferation while enhancing invasion through metabolic reprogramming from oxidative phosphorylation to glycolysis. Our study reveals spatially co-localized niches forming a \"pro-tumorigenic triad\" and identifies HMGA2-regulated Hypoxic CAFs associated with metabolic-driven phenotypic switching as candidate therapeutic targets for spatially informed CRC intervention.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"226-242"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771600","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":"Phase I multi-center clinical and biomarker study of the dual-action androgen receptor inhibitor ONCT-534.","authors":"Matthew R Chrostek, James Robinson, Rajesh Krishnan, Evan Y Yu, Luke T Nordquist, Andrae L Vandross, Mohamad A Salkeni, Jennifer Schehr, Matthew Mannino, Alyssa Hintz, Jacob Caceres, Manushi Vatani, Hamid Emamekhoo, Peter Nelson, Chris Markey, Elisabeth Coates, James Breitmeyer, Lawrence Fong, Johann S De Bono, Joshua M Lang, Shuang G Zhao","doi":"10.1007/s10637-026-01600-8","DOIUrl":"10.1007/s10637-026-01600-8","url":null,"abstract":"<p><p>ONCT-534 is a dual-action androgen receptor inhibitor (DAARI) that combines AR antagonism and degradation via N-terminal domain binding, additionally targeting AR splice variants. In this study patients received ONCT-534 daily ranging from 40 to 1200 mg. The primary objectives were safety and dose-limiting toxicities (DLTs). Additional objectives included antitumor activity and AR signaling biomarkers. Adverse events (AEs) were assessed within the first 28 days for DLTs. Clinical activity was evaluated by PSA and radiographic progression per PCWG3 and RECIST v1.1. The trial was stopped early and not all patients were evaluated per protocol. Twenty-one patients received ONCT-534 across six doses. The most common AEs were anemia, back pain, and fatigue. While no DLTs were observed within 28 days, Grade 3/4 AEs occurred later in 9 patients (anemia most frequently). One patient discontinued due to treatment-related AE. No radiographic or PSA-based responses were observed; however, three patients showed PSA declines at week 4, with one achieving a PSA50 at time of study closure. Of 10 patients with baseline AR protein data, the median change was - 40.59% in AR protein levels at week 4. In the 300 mg cohort, 3 patients showed concordant decreases in AR protein and AR gene expression. Here, PSA levels correlated positively with AR target gene and AR gene expression. ONCT-534 had acceptable safety and demonstrated biological activity through AR protein degradation and AR signaling suppression in mCRPC patients. Although clinical responses weren't observed, these findings provide proof-of-concept for examining AR protein changes in patients receiving DAARIs.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"103-112"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13292475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network pharmacology-based therapeutic intervention of Mentha arvensis targeting cancer and doxorubicin-induced cardiotoxicity.","authors":"Satinder Kaur, Umashanker Navik, Gurjit Kaur Bhatti, Jasvinder Singh Bhatti","doi":"10.1007/s10637-026-01595-2","DOIUrl":"10.1007/s10637-026-01595-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Doxorubicin (Dox) is a widely used chemotherapeutic agent effective against hematological malignancies and solid tumors, including leukemia, breast and bladder cancers, lymphomas, and Kaposi's sarcoma. Despite its clinical efficacy, the therapeutic application of Dox is severely limited by dose-dependent cardiotoxicity, manifesting as both acute and chronic Doxorubicin-induced cardiotoxicity (DIC). Dexrazoxane (Dexa) remains the only FDA-approved cardioprotective agent available; however, it compromises the anti-cancer activity of Dox and poses risks such as secondary malignancies, particularly in pediatric patients. This unmet clinical challenge underscores the urgent need for safer and more effective therapeutic strategies that preserve the anticancer potency of Dox while preventing or minimizing doxorubicin-induced cardiotoxicity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A network pharmacology-based strategy was adopted to screen phytochemicals of Mentha arvensis. Compounds were filtered based on plasma bound fraction and volume of distribution by Deep-PK. Protein-protein interaction (PPI) networks and hub gene analyses were performed to determine key targets common to DIC and cancer. Molecular docking studies evaluated the interactions of phytochemicals alone and in combination with Dexa against critical targets implicated in both cancer and cardiotoxicity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 39 phytochemicals were screened including Methyl acetate, p-Menthan-3-one, trans-Linalool, Piperitone, Octyl acetate, Camphor, Dihydrocarveol, p-Menthan-3-one, Furfural, Menthol, 3-Octyl acetate, 3-Octanone, 2-Hexen-1-OL, DL-Borneol, Piperitenone Oxide, alpha-Terpineol, 2-Hexenal, beta-Terpineol, Myrtenal, cis-3-Hexen-1-ol, Myrtenol, Isoamyl alcohol, 1-Hexanol, Lavandulyl acetate, Citral, Neral, Linalyl acetate, 1-Octanol, 3-Nonanol, (+ -)-Linalool, 1,8-Cineole, Citronellol, 1-Octen-3-OL, Nonanol, Geranyl acetate, Neryl acetate, 1-Decanol, 4-Terpineol and Geraniol. Based on prior in vivo validation in cancer and DIC models, Linalool, Geraniol and Citronellol were further selected for Docking. Among these, Citronellol emerged as a promising compound that can be used in combination with Dexa without compromising anti-cancer efficacy of Dox and Cardioprotective action of Dexa. TNFA, MMP2, PTGS2, JUN and HMOX1 identified as common targets between cancer and DIC with alone phytochemicals of M. arvensis. However, the key shared targets identified in both cancer and DIC alongwith phytochemicals and Dexa included TNFA, ACE, SIRT1, CDK2, and AKR1B1.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Phytochemicals derived from Mentha arvensis demonstrate potential as dual-action agents capable of mitigating doxorubicininduced cardiotoxicity while preserving anticancer activity. However, when used alone, these compounds exhibited only moderate therapeutic potential. Combinatorial strategies involving Dexa may enhance cardioprotective efficacy while r","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"135-173"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390099","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":"Recent progress of dendritic cell-derived exosomes in tumor immunotherapy.","authors":"Baiyan Wang, Yirui Hu, Yujia Zhou, Qianqian Han, Yu Huang, Yuanhang Dong, Yike Zhang, Zixuan Guo, Xuan Zhang, Shuying Feng","doi":"10.1007/s10637-026-01604-4","DOIUrl":"10.1007/s10637-026-01604-4","url":null,"abstract":"<p><p>Despite advancements in conventional tumor therapies including surgery and chemotherapy, effective cancer management remains challenging due to treatment resistance and tumor microenvironment complexity. Dendritic cell (DC)-based vaccines, while representing a milestone in tumor immunotherapy, face clinical limitations such as poor viability and limited antigen presentation capacity. Importantly, dendritic cell-derived exosomes (DEXs) have emerged as a potential alternative. In contrast to DC vaccines, DEXs possess excellent in vivo biocompatibility and biosafety, demonstrate higher immunogenicity, exhibit stronger immunosuppressive resistance, and require lower production costs. Mechanistically, DEXs overcome immunosuppressive obstacles through dual delivery of immunostimulatory cargo and tumor-associated antigens, thereby achieving superior anti-tumor effects. This review examines recent research progress regarding DEXs in tumor immunotherapy, with particular emphasis on their roles in immune activation, the regulation of the tumor microenvironment, serving as drug delivery vehicles, and vaccine development. These advancements will help deepen the understanding of tumor immunotherapy and promote clinical translation.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"196-210"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638811","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}