Investigational New Drugs最新文献

{"title":"Crocetin suppresses colorectal cancer progression by targeting TGM2 and inhibiting the JAK2/STAT3 pathway.","authors":"Shuo Chen, Weijun Su, Kai Wang, Mingyue Xu, Binjie Su","doi":"10.1007/s10637-026-01608-0","DOIUrl":"10.1007/s10637-026-01608-0","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a major health threat with limited therapies for advanced stages. Crocetin, a natural compound from saffron, has broad anticancer potential, but its mechanisms in CRC are unclear.</p><p><strong>Methods: </strong>A CRC xenograft mouse model was established to evaluate the antitumor effect of crocetin. Next, transcriptomic analysis was performed to identify differentially expressed genes (DEGs) in tumor tissues of tumor-bearing mice between the crocetin treatment and control groups. Through the integration of network pharmacology, and protein-protein interaction (PPI) network analysis, potential key target genes regulated by crocetin in CRC were identified. Functional assays (e.g. CCK-8 and transwell assays) were employed to assess the biological role of crocetin and its target gene, TGM2, in CRC cells.</p><p><strong>Results: </strong>Crocetin significantly inhibited tumor growth in HCT116-tumor-bearing mice in vivo. Transcriptomic analysis identified 2,577 DEGs in tumor tissues between the crocetin and control groups. Through integrated network pharmacology, transcriptomics, and molecular docking analyses, we identified five potential crocetin-targeted genes-ADAM17, DNMT1, MTOR, TGM2, and XRCC6-all of which showed significant downregulation following crocetin treatment. Furthermore, in vitro experiments demonstrated that crocetin notably suppressed cell viability, migration, and invasion, as well as reduced the expression of TGM2, p-JAK2, and p-STAT3 in HCT116 cells; however, the tumor-suppressive effects of crocetin were markedly abolished by TGM2 overexpression.</p><p><strong>Conclusion: </strong>Collectively, crocetin could suppress CRC progression by targeting TGM2/JAK2/STAT3 signaling pathway, supporting its potential as a therapeutic agent for CRC.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"174-186"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147457557","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":"Transforming cisplatin therapy: a localized, injectable poly(anhydride-ester) depot for safer and more effective head and neck cancer treatment.","authors":"Omiya Ali Hasan, Randa Mohammed Zaki, Obaid Afzal, Yasser Zaki, Mahmoud Omar, Amany A Abdel-Rheem","doi":"10.1007/s10637-026-01597-0","DOIUrl":"10.1007/s10637-026-01597-0","url":null,"abstract":"<p><p>Head and neck cancer patients often receive systemic cisplatin chemotherapy, which is effective but limited by severe toxicity and poor tumor selectivity. An injectable, biodegradable polyanhydride polymer derived from sebacic acid (SA) and ricinoleic acid (RA) was investigated as a localized carrier for cisplatin to improve its safety and efficacy. Cisplatin was loaded into a poly(SA-RA) polymer at 1% and 10% (w/w) concentrations. The 10% formulation (\"TumoCure\") was evaluated for safety and pharmacokinetics via subcutaneous administration in rats and intramuscular administration in pigs. Efficacy was assessed using a diluted 1% cisplatin formulation, administered intratumorally in a FaDu human head-and-neck squamous cell carcinoma xenograft model in mice. In vitro studies demonstrated sustained cisplatin release from the polymer over several weeks, a release profile that correlated well with in vivo kinetics and followed an apparent first-order pattern. In the mouse tumor model, intratumoral injection of the 1% polymer-cisplatin formulation produced dose-dependent tumor growth inhibition with prolonged local drug activity. In contrast, systemic cisplatin administration resulted in early tumor regrowth and significant toxicity. The polymer-based treatment caused no observable systemic toxicity or weight loss, with only localized, transient tissue reactions noted at the injection sites. The cisplatin-loaded poly(SA-RA) matrix provides controlled release and enhanced local efficacy in head and neck tumor models, with minimal systemic side effects supported by a tenfold reduction in systemic drug exposure. These results support the potential of this injectable, biodegradable polymer formulation as a safer and more effective alternative to systemic cisplatin for patients with locally advanced head and neck carcinoma, particularly those who are unfit for or have contraindications to systemic chemotherapy.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"121-134"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390090","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":"Prognostic factors and outcome measures after BRAF-directed targeted therapy of unresectable metastatic BRAF^V600E colorectal cancer: a study cohort-level analysis.","authors":"Giuseppe A Colloca, Antonella Venturino","doi":"10.1007/s10637-026-01607-1","DOIUrl":"10.1007/s10637-026-01607-1","url":null,"abstract":"<p><p>BRAF^V600E mutation in metastatic colorectal cancer (mCRC) is associated with a poor prognosis. BRAF^V600E inhibitors (BRAFi) plus EGFR inhibitors + / - MEK inhibitors regimens prolonged overall survival (OS), but prognosis remains heterogeneous and intermediate endpoints' reliability after BRAFi-based regimens has been poorly evaluated. The purpose of the study is to investigate the relationship of baseline variables and intermediate endpoints with OS in studies of BRAFi-based regimens. A literature search was conducted to identify clinical trials reporting the outcome of mCRC patients receiving a BRAFi-based regimen. The relationship of each baseline variable and of the intermediate endpoints with OS was calculated by linear regression, separately for the most frequently reported of variables and for progression-free survival (PFS), objective response rate (ORR), or disease control rate (DCR). Finally, the effect of the prognostic baseline variables on the relationship of intermediate endpoints with OS was evaluated. Twelve articles (17 study cohorts) were eligible, and seven variables were reported in at least 15 study cohorts. Older age and microsatellite instability-high (MSI) status were inversely related to longer survival, with MSI maintaining its prognostic effect even in the cohorts receiving BRAFi plus EGFR inhibitor (adjusted R² = 0.317; β =  - 0.239; p-value = 0.033). All intermediate endpoints showed a significant relationship with OS. After adjusting for MSI, the relationship of DCR with OS significantly improved, whereas the changes in the relationship of ORR and PFS with OS were not significant.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"113-120"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372514","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 pharmacokinetic characteristics and the food effect of radotinib.","authors":"Yerin Lee, Jiwon Kim, Minseo Kang, Jiwon Han, Na Yun Kim, Jae Soo Shin, Min Soo Park, Qian Jiang, Jangik I Lee","doi":"10.1007/s10637-026-01610-6","DOIUrl":"10.1007/s10637-026-01610-6","url":null,"abstract":"<p><p>Radotinib is a second-generation tyrosine kinase inhibitor that selectively targets BCR-ABL1 and is used for the treatment of chronic myeloid leukemia (CML). This study aimed to evaluate the clinical pharmacokinetic characteristics and the food effect of radotinib. Healthy volunteers received a single oral dose of radotinib 400 mg under fasted or fed conditions in a crossover manner, and CML patients received repeated oral doses of 300 mg twice daily. The pharmacokinetic characteristics were evaluated by a noncompartmental method, using plasma concentration-time data following a single administration in healthy volunteers, and on Days 1 and 14 in CML patients. The food effect was assessed by comparing the pharmacokinetic parameters under fed and fasted conditions in healthy volunteers. The pharmacokinetic analyses of radotinib included data from 23 healthy male volunteers and 24 patients newly diagnosed with CML. In both populations, the plasma concentrations of radotinib peaked at approximately 3 h. In healthy volunteers, the concentrations declined biexponentially with the terminal half-life (t_1/2) of 17.5 h under fasted conditions. In CML patients, radotinib was substantially accumulated with the accumulation ratio of 3.59 on Day 14. The effective t_1/2 derived from the accumulation ratio was 25.5 h. The systemic exposure to radotinib increased by 3.49-fold when administered after food intake, with time to maximum concentration delayed by 3 h. The results of the study provide essential pharmacokinetic information for the clinical use of radotinib in the treatment of CML patients. ClinicalTrials.gov, Identifier NCT06461078, NCT03722420.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"187-195"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147529164","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":"Selective cytotoxicity of solamargine via oxidative stress and caspase-independent mechanisms in human glioblastoma cells.","authors":"Arthur Barcelos Ribeiro, Marcela de Melo Junqueira, Ricardo Andrade Furtado, Jairo Kenupp Bastos, Denise Crispim Tavares","doi":"10.1007/s10637-026-01599-y","DOIUrl":"10.1007/s10637-026-01599-y","url":null,"abstract":"<p><p>IDH-wild-type glioblastoma (IDH-wildtype GB) is an aggressive and genetically heterogeneous tumor characterized by intrinsic resistance to radiotherapy and chemotherapy, while surgical resection remains inherently limited by its diffuse infiltrative growth, leading to poor clinical outcomes. Natural products such as solamargine (SM), a steroidal glycoalkaloid with cytotoxic and antitumor properties, have emerged as potential adjuvant strategies. Here, we investigated the effects of SM on proliferation, clonogenic survival, morphology and migration of IDH-wildtype GB cell lines (U-87MG, U-251MG and T98-G) and non-tumoral astrocytes under normoxic and hypoxic conditions, as well as its interaction with temozolomide (TMZ). Under normoxia, SM reduced cell viability in a dose- and time-dependent manner, with IC₅₀ values between 5.04 and 9.53 μM and showed enhanced cytotoxicity under hypoxia. TMZ alone displayed modest activity, and its combination with SM produced predominantly antagonistic effects. Clonogenic assays confirmed the antiproliferative potential of SM, with significant inhibition of colony formation at 2.5 μM. SM induced marked morphological alterations but did not significantly impair migration in wound-healing assays. In U-87MG cells, SM triggered G₂/M cell-cycle arrest, increased intracellular reactive oxygen species generation, and elevated γH2AX protein expression, indicating oxidative stress-associated DNA damage. However, cleaved caspase-3 and p53 were not detected, suggesting a predominantly non-apoptotic mode of cell death. Together, these findings support SM as a promising candidate for IDH-wildtype GB therapy and underscore the need for further studies to clarify its mechanisms of action and optimize its therapeutic use.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"39-47"},"PeriodicalIF":3.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124743","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":"Design, synthesis, anticancer activity, bioimaging, and molecular docking of novel fluorescent isatin derivatives.","authors":"Merve İnel, Ayse Yildirim, Mustafa Yilmaz, Bahadir Ozturk","doi":"10.1007/s10637-026-01601-7","DOIUrl":"10.1007/s10637-026-01601-7","url":null,"abstract":"<p><p>Breast cancer remains a leading global health challenge, driving the urgent need for innovative therapeutic strategies. This study presents the initial results of the design, synthesis, characterization, and in vitro evaluation of a novel fluorescent agent for breast cancer treatment, focusing on its subcellular localization and molecular docking. Seven novel fluorescent compounds (3a-g) were synthesized via isatin derivatives and 4-bromo 1,8-naphthalimide conjugation. The compounds were spectroscopically characterized and tested in MDA-MB-231 and MCF-7 cells using viability assays, Annexin-V and propidium iodide flow cytometry to define cytotoxic mechanisms, confocal microscopy with nuclear and mitochondrial markers for subcellular localization, and molecular docking to VEGFR2 (4AGD) and KIT (3G0E) as co-crystals. 3a (3,85 µM and 2,99 µM) and 3c (1,77 µM and 77,31 µM) emerged as two candidates with high cytotoxic potential, exhibiting the lowest IC₅₀ values in MCF-7 and MDA-MB-231 cell lines, respectively, at the 24^th hour. Several conjugates, particularly 3a (87.47 %) and 3 g (96.62 %) in MCF-7, induced late apoptosis, and 3c (98.57 %) in MDA-MB-231 induced the highest early apoptosis. Across both proteins (3G0E and 4AGD), 3c consistently shows stronger predicted binding than sunitinib, with more negative binding energies and lower Ki values in each case, supporting its promise as a lead together with 3a.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"9-22"},"PeriodicalIF":3.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052041","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 mechanistic role of Wilms tumor 1-associated protein in cancer pathogenesis, immunity, immunotherapy, and therapy resistance.","authors":"Sarah Qutayba Badraldin, Karar H Alfarttoosi, Hayder Naji Sameer, Ashok Kumar Bishoyi, Subbulakshmi Ganesan, Aman Shankhyan, Subhashree Ray, Deepak Nathiya, Ahmed Yaseen, Zainab H Athab, Mohaned Adil","doi":"10.1007/s10637-026-01606-2","DOIUrl":"10.1007/s10637-026-01606-2","url":null,"abstract":"<p><p>Wilms' tumor 1-associated protein 1 (WTAP) is an epitranscriptomic regulator with multifaceted roles in cancer biology. Acting beyond its function in the m6A methyltransferase complex, WTAP governs RNA splicing, stability, and translation, influencing oncogenic signaling, immune modulation, and therapy resistance. Recent evidence reveals its dynamic involvement in diverse malignancies, where it can act as both an oncogene and tumor suppressor depending on the cellular context. WTAP promotes tumor progression through epithelial-mesenchymal transition (EMT), metabolic reprogramming, angiogenesis, and immune evasion, and contributes to resistance against chemotherapy and immunotherapy by regulating DNA repair, ferroptosis, and immune checkpoint pathways. However, studies have also demonstrated that WTAP can exert tumor-suppressive effects under specific physiological conditions, such as hepatocyte-specific WTAP loss leading to extracellular-signal regulated kinases (ERK)-driven hepatocarcinogenesis, and WTAP-mediated m6A regulation restraining oncogenic signaling in some prostate cancers. Moreover, by enhancing ferroptosis resistance, WTAP may weaken ferroptosis-driven antitumor immunity and contribute to immune-checkpoint resistance. Understanding these mechanisms offers opportunities for exploiting WTAP as a biomarker and therapeutic target across multiple cancer types. This review explores the multifaceted role of WTAP in cancer, focusing on its mechanisms of action in tumorigenesis, immune modulation, and therapy resistance, and offers insights into potential therapeutic strategies targeting WTAP in cancer treatment.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"64-89"},"PeriodicalIF":3.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131014","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":"Patient-derived tumor organoids for new drug development: promises and challenges.","authors":"Meijun He, Ying Wu, Furong Du, Jingrui Wang, Honghan Zhang, Jian Han","doi":"10.1007/s10637-026-01605-3","DOIUrl":"10.1007/s10637-026-01605-3","url":null,"abstract":"<p><p>The development of antitumor drugs is affected by various unfavorable factors, including long cycles of research and development, large differences in drug efficacy in vivo, and efficacy differences in individuals. Patient-derived tumor organoids (PDTOs), a novel preclinical model in cancer research, are three-dimensional microstructures differentiated from stem cells, with the capability of self-organizing into micro-organs that resemble the original tumor tissues. They have been demonstrated to faithfully recapitulate the biological and molecular features of the original tumor while preserving the tumor heterogeneity. Recently, PDTOs show great potential in drug screening and new drug development. In this review, we overviewed the types of organoids, application of PDTOs in developing new drugs, as well as their challenges and opportunities to provide powerful insights into drug development.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"90-102"},"PeriodicalIF":3.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194454","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 novel aurora kinase molecular glue-based degrader sp-2-067 inhibits prostate cancer cell growth and alters immune profile.","authors":"Sanjeev Shukla, Sarah Pogash, Arjun Venkatesh, Joseph McGrath, Reynier D Rodriguez Rosales, Jean-Pierre Kanumuambidi, Mohammed Al-Toubat, Steven Fletcher, K C Balaji","doi":"10.1007/s10637-026-01603-5","DOIUrl":"10.1007/s10637-026-01603-5","url":null,"abstract":"<p><p>Aurora Kinase A (AKA) is overexpressed in prostate cancer and promotes disease progression through oncogenic pathways and immune modulation. AKA inhibition faces challenges in clinical trials, and alternate methods, such as degradation, may overcome some of these barriers. We evaluated SP-2-067, a novel selective AKA degrader, in C4-2 prostate cancer cells using viability assays, Western blot analysis, and siRNA knockdown. SP-2-067's dose- and time-dependent effects on AKA, related proteins (AUNIP and NINEIN) and immune checkpoint (IC) proteins (PD-L1 and LAG3) were quantified. In silico analysis of TCGA datasets examined the clinical link of the AKA axis and its correlation with immune cell infiltration in prostate cancer. SP-2-067 demonstrated potent dose-dependent anti-proliferative effects. The compound selectively degraded AKA over Aurora Kinase B (AKB) with sustained effects at 72 h. Treatment induced marked PD-L1 upregulation (~ 20-fold at 3 h) and concurrent LAG3 downregulation. siRNA experiments confirmed these effects were AKA-dependent. TCGA analysis revealed AKA, AUNIP, and NINEIN overexpression in prostate cancer correlates with distinct immune-cell infiltration. SP-2-067 is a novel, selective AKA degrader that modulates IC expression by upregulating PD-L1 and downregulating LAG3, indicating its potential for immunomodulation through AUNIP- and NINEIN-mediated mechanisms. Additionally, AKA, AUNIP, and NINEIN are linked to a distinct immune cell profile, presenting an opportunity to reshape the tumor immune microenvironment and support combinatorial strategies with IC inhibitors in prostate cancer.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"56-63"},"PeriodicalIF":3.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258069","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":"Scorpio fuscus venom as a promising anticancer agent against colorectal cancer.","authors":"Serdar Karakurt, Cigdem Gokcek-Sarac, Sinan Kandir, Irem Mukaddes Bilgiseven, Ersen Aydın Yagmur, Hasan Ufuk Celebioglu","doi":"10.1007/s10637-026-01598-z","DOIUrl":"10.1007/s10637-026-01598-z","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, underscoring the urgent need for novel and effective therapeutic agents. Conventional treatments, including chemotherapy, radiotherapy, and surgery, are often associated with significant adverse effects, prompting the exploration of alternative therapeutic strategies. This study aimed to evaluate the anticancer effects of Scorpio fuscus venom (SFV) on human colorectal cancer models using integrated in vitro and in vivo approaches. SFV constituents were characterized using gel electrophoresis, followed by high-performance liquid chromatography and UV-visible spectrometry. Identified peptides were subjected to structural modeling and in silico docking analyses against selected proteins associated with colorectal cancer and apoptosis-related pathways. The cytotoxic effects of SFV were assessed in human CRC cell lines (DLD-1, HT-29, and CaCo-2) and a healthy colon epithelial cell line (CCD-18Co) using Alamar Blue assays after 48-h treatment, and half-maximal inhibitory concentration (IC₅₀) values were determined. SFV treatment resulted in a dose-dependent reduction in cancer cell viability, accompanied by decreased migratory capacity and colony formation ability. Apoptotic responses were further evaluated by flow cytometry and gene expression analyses, indicating modulation of apoptosis-associated genes. For in vivo validation, subcutaneous and orthotopic xenograft colon cancer models were established in mice. SFV administration led to reduced tumor growth compared with control groups. Immunohistochemical analyses revealed altered expression patterns of selected tumor-related markers in SFV-treated tumors. Gene expression profiling demonstrated ≥ twofold changes in 51 genes, including downregulation of BAK1 and TRAF3, and upregulation of BIRC2, BIRC3, BIRC6, CASP8, TNFRSF8, TNFRSF11, and BOK. Collectively, these findings indicate that SFV exerts significant antitumor effects in colorectal cancer models and support its potential as a promising anticancer agent, warranting further mechanistic and translational investigation.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":" ","pages":"23-38"},"PeriodicalIF":3.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105485","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}