Cancer Chemotherapy and Pharmacology最新文献

{"title":"Therapeutic modulation of the blood-brain barrier in brain tumors: a systematic review of clinical and translational approaches.","authors":"Jheremy S Reyes, Sofia-Isabella Leal, Juan S Aguirre, Raul F Vega-Alvear, Jheremy E Reyes-Castellanos","doi":"10.1007/s00280-026-04888-8","DOIUrl":"10.1007/s00280-026-04888-8","url":null,"abstract":"<p><p>PURPOSE: The blood–brain barrier (BBB) is a major obstacle to effective treatment in neuro-oncology, as it limits the penetration of therapeutic agents into tumors of the central nervous system. This systematic review aimed to systematically synthesize clinical and translational evidence on BBB modulation for enhanced drug delivery in brain tumor therapy, with emphasis on clinical outcomes, intratumoral exposure and mechanistic pharmacodynamic endpoints. METHODS: A systematic search was conducted in PubMed and ScienceDirect from January 2000 to December 2025, following PRISMA guidelines. We included clinical and translational research, such as randomized controlled trials, cohort studies, and case series, that assessed techniques to disrupt the blood–brain or blood–tumor barrier. Main strategies included intra-arterial osmotic disruption, low-intensity focused ultrasound, laser interstitial thermal therapy, pharmacological modulation, and nanotechnology-based delivery systems. Efficacy, safety, and pharmacokinetics were evaluated. RESULTS: Twenty-five studies were included. Osmotic disruption with intra-arterial mannitol remains the most studied approach, showing enhanced intratumoral drug concentration and potential survival benefits. Focused ultrasound has emerged as a non-invasive, repeatable method with immunomodulatory effects. Laser interstitial therapy facilitates temporary barrier disruption. Pharmacological agents like AZD1775 and Trotabresib, and targeted systems such as immunoliposomes, showed variable central nervous system penetration. Biomarkers and imaging parameters, such as transthyretin and Ktrans, were used to assess barrier permeability. CONCLUSION: Therapeutic disruption of the blood–brain barrier is a promising strategy to enhance intratumoral drug delivery in brain tumors. Further clinical trials and biomarker validation are needed to optimize safety and efficacy. </p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durable response to brigatinib in a ROS1 fusion-positive inflammatory myofibroblastic tumor.","authors":"Gabriela Alamilla-García, Oscar Tahuahua-Flores, Alejandro Soriano-Maya, Enrique Caballé-Pérez, Claudia Haydee Sarai Caro-Sánchez, Dorian Yarih García-Ortega","doi":"10.1007/s00280-026-04886-w","DOIUrl":"10.1007/s00280-026-04886-w","url":null,"abstract":"<p><p>Inflammatory myofibroblastic tumor is an ultra-rare mesenchymal neoplasm of intermediate malignant potential, characterized by oncogenic rearrangements involving ALK (50–60%), ROS1 (5–10%), and less commonly NTRK3 or RET. We report a 32-year-old woman with an unresectable pulmonary tumor harboring a TFG–ROS1 fusion who achieved a durable partial response to brigatinib, sustained for more than 12 months. Histopathologic evaluation revealed a low-grade spindle-cell neoplasm lacking ALK expression, and genomic profiling identified the actionable fusion. This case highlights how molecular characterization can refine the management of ultra-rare sarcomas, enabling anatomically constrained disease to become targetable and underscoring the role of tumor biology in therapeutic decision-making.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: High MCM10 expression mediates TMZ resistance and promotes the progression of glioma.","authors":"Qiusi Tian, Zhijun Bao, Yifei Zhao, Qun Zhang","doi":"10.1007/s00280-026-04873-1","DOIUrl":"10.1007/s00280-026-04873-1","url":null,"abstract":"","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why are we still using cisplatin? : Rationale for the continued use of cisplatin in oncology.","authors":"Jemma Arakelyan, Herbert Loong, Robert Peter Gale, Chi-Ming Che","doi":"10.1007/s00280-026-04882-0","DOIUrl":"10.1007/s00280-026-04882-0","url":null,"abstract":"<p><p>Although numerous novel cancer therapies have been introduced over the past five decades, cisplatin remains central to curative treatment for several major cancers, including testicular, ovarian, lung, and head and neck malignancies. The persistence of cisplatin use, despite its well-documented and often severe toxicities, constitutes a critical and unsolved paradox in oncology. Here, we examine this paradox by analyzing the economic, clinical, biological, and chemical factors that have entrenched cisplatin’s role and delayed its replacement.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing of dose reduction matters: interpreting survival outcomes with CDK4/6 inhibitors in advanced breast cancer.","authors":"Kadri Altundag","doi":"10.1007/s00280-026-04879-9","DOIUrl":"https://doi.org/10.1007/s00280-026-04879-9","url":null,"abstract":"","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ribociclib is not a substrate or inhibitor of Oatp1b-mediated uptake in vivo.","authors":"Thomas Drabison, Eman A Ahmed, Nathan Colasanti, Robert H Weber, Alex Sparreboom, Eric D Eisenmann","doi":"10.1007/s00280-026-04877-x","DOIUrl":"10.1007/s00280-026-04877-x","url":null,"abstract":"<p><strong>Purpose: </strong>Ribociclib is a CDK4/6 inhibitor used to treat HR+/HER2- breast cancer. Despite regulatory documents suggesting that ribociclib may inhibit both CYP3A and OATP1B-type transport in vitro, it is unclear whether CDK4/6 inhibitors interact with these mechanisms in vivo. Based on two cases of severe rhabdomyolysis in patients taking a CDK4/6 inhibitor and simvastatin, a CYP3A and OATP1B substrate, we tested the hypothesis that CDK4/6 inhibitors may precipitate drug-drug interactions through these mechanisms.</p><p><strong>Methods: </strong>We assessed the ability of CDK4/6 inhibitors to inhibit CYP3A and OATP1B-type transporters. Based on these data, we performed pharmacokinetic studies and toxicity assessments to determine whether ribociclib is a substrate or inhibitor of OATP1B-type transport in vivo.</p><p><strong>Results: </strong>Ribociclib inhibited the metabolism of triazolam, a CYP3A probe, in vivo. Additionally, CDK4/6 inhibitors inhibited OATP1B-type transporters in vitro. However, ribociclib, the most potent OATP1B inhibitor, did not influence the pharmacokinetics or pharmacodynamics of the OATP1B substrates CDCA-24G or paclitaxel. Furthermore, Oatp1b2 deficiency did not alter the pharmacokinetics of ribociclib.</p><p><strong>Conclusion: </strong>Our findings suggest that clinically significant OATP1B-mediated interactions are not anticipated with CDK4/6 inhibitors, either as victims or perpetrators, which supports ongoing clinical trials investigating the co-administration of CDK4/6 inhibitors with OATP1B substrates and inhibitors.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temozolomide resistance in glioma: aligning target discovery with clinically achievable CNS exposures and translational delivery strategies.","authors":"M Vijayasimha","doi":"10.1007/s00280-026-04878-w","DOIUrl":"https://doi.org/10.1007/s00280-026-04878-w","url":null,"abstract":"","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population pharmacokinetics of encorafenib and binimetinib in real-world patients with BRAF^V600E/K-mutant metastatic melanoma.","authors":"Yuan J Pétermann, Alicja Puszkiel, Abbas Khani, Nora Kramkimel, Elisa Funck-Brentano, Benédicte Oules, Sarah Bouchereau, Michel Vidal, Xavier Decleves, Chantal Csajka, Benoit Blanchet, Monia Guidi","doi":"10.1007/s00280-026-04876-y","DOIUrl":"10.1007/s00280-026-04876-y","url":null,"abstract":"<p><p>PURPOSE: Encorafenib and binimetinib pharmacokinetic (PK) studies in real-world cancer patients remain scarce. We aimed to characterize their population pharmacokinetics (popPK) in routine clinical care and compare real-life exposure metrics with clinical trials data. METHODS: We conducted population pharmacokinetic (popPK) analyses in real-world patients with BRAFV600E/K-mutant metastatic melanoma to characterize interindividual variability (IIV) and identify significant covariates in MonolixSuite™. Final model-based Bayesian individual PK metrics (i.e., trough concentration, Cmin, maximal concentration, Cmax, unbound average concentration, Caverage, and area under the curve, AUCτ) were compared with data from clinical trials and potency-anchored metrics (reported half-maximal inhibitory concentration, IC50). RESULTS: Data from 66 encorafenib and 69 binimetinib patients (310 and 311 samples) were analyzed. For both drugs, a two-compartment model with first-order absorption and linear elimination best described the data. None of the studied covariates were significantly associated with model parameters. Model-predicted PK metrics (geometric mean and CV(%)) for encorafenib and binimetinib at 450 mg QD and 45 mg BID were: Cmin 19 ng/mL (73%) and 55 ng/mL (56%), Cmax 3378 ng/mL (30%) and 367 ng/mL (24%), and half-lives 12.5 h (95%) and 7.3 h (67%), respectively. Encorafenib AUC24h was 15,785 ng·h/mL (17%) and binimetinib AUC12h was 2003 ng·h/mL (22%). Monte Carlo simulation showed that reducing encorafenib from 450 mg to 300 mg once daily lowered unbound Caverage by 33% while maintaining substantial coverage relative to IC50. CONCLUSION: Overall, these metrics are comparable to those reported in clinical trial data. This population PK model could be useful to explore the exposure-response relationship in future PK/PD studies. </p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Anlotinib combined with temozolomide suppresses glioblastoma growth via mediation of JAK2/STAT3 signaling pathway.","authors":"Peng Xu, Handong Wang, Hao Pan, Jiakai Chen, Chulei Deng","doi":"10.1007/s00280-026-04874-0","DOIUrl":"10.1007/s00280-026-04874-0","url":null,"abstract":"","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KAT2B-mediated epigenetic suppression of RAD51C enhances olaparib sensitivity in colorectal cancer.","authors":"Xiaoqin Liu, Jun Chen, Xuwei Shen, Lin Li","doi":"10.1007/s00280-026-04872-2","DOIUrl":"10.1007/s00280-026-04872-2","url":null,"abstract":"<p><strong>Introduction: </strong>By blocking poly ADP ribose polymerase (PARP), olaparib decreases the proliferation of tumours by preventing DNA damage repair, particularly in tumours that have BRCA1/2 mutations or are BRCA-negative. However, a phase II study of 33 CRC patients receiving mono-olaparib therapy revealed that some of these individuals still had resistance to olaparib therapy but had poor DNA damage repair ability. RAD51C reversion mutation is a frequent reason for the resistance of cancers with BRCA mutations to PARP inhibitors.</p><p><strong>Methods: </strong>Here, we introduce K(lysine)-acetyltransferase 2B (KAT2B) as a protein involved in the transcription of RAD51C, reducing the expression of RAD51C by lowering the acetylation of histone H3 (H3K27) at the promoter of RAD51C.</p><p><strong>Results: </strong>We found that a subset of tumour cells expressing RAD51C presented reduced endogenous KAT2B expression, which led to increased accumulation of DNA damage (increased γH2AX accumulation), and lower KA2TB expression decreased PARPi resistance in RAD51C-expressing cells. These findings indicate that colorectal cancer cells with lower KAT2B and RAD51C levels are more vulnerable to olaparib therapy. Our findings indicate that PARPi responses and the expression of RAD51C are significantly regulated by KAT2B and histone acetylation.</p><p><strong>Conclusion: </strong>These results offer vital and novel insights into the combination of inhibitors in patients who are resistant to olaparib therapy, especially patients with RAD51C reversion mutations.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12987815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}