Cancer Chemotherapy and Pharmacology最新文献

{"title":"Outcomes of locally produced donor-derived anti-CD19 chimeric antigen receptor T-cells in relapsed or refractory B-cell acute lymphoblastic leukemia patients.","authors":"Supavich Tannumsaeng, Usanarat Anurathapan, Arpatsorn Sermcheep, Pattara Kanjanakan, Chayamon Takpradit, Kleebsabai Sanpakit, Pimjai Niparuck, Thanakrit Piyajaroenkij, Adisak Tantiworawit, Korakot Atjanasuppat, Piamsiri Sawaisorn, Sarinthip Preedagasamzin, Bunyada Jittorntrum, Somsak Prasongtanakij, Samart Pakakasama, Suradej Hongeng","doi":"10.1007/s00280-026-04952-3","DOIUrl":"https://doi.org/10.1007/s00280-026-04952-3","url":null,"abstract":"<p><p>Donor-derived anti-CD19 chimeric antigen receptor T-cell (CAR T-cell) therapy has emerged as one of the most promising treatments for relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). In this retrospective study, we evaluated the safety and efficacy of donor-derived anti-CD19 CAR T cells manufactured at our local GMP-compliant production facility. Eleven patients with R/R B-ALL received donor-derived anti-CD19 CAR T-cell therapy. Seven of the eleven patients had previously undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). All eleven patients achieved minimal residual disease (MRD) negativity by day 28 post-infusion. Three patients developed grade 1 cytokine release syndrome (CRS), and one patient developed grade 2 CRS. No case of immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. The patient who experienced grade 2 CRS also developed grade 2 graft-versus-host disease (GVHD. At the median follow-up time of 47 months (range, 6-104 months), eight patients remained alive and MRD-negative. Three patients died: one from bone marrow (BM) relapse, one from concurrent BM and central nervous system (CNS) relapses, and one from candidemia. The 5-year overall survival and event-free survival rates were both 70%. In this retrospective study, donor-derived anti-CD19 CAR T-cells produced in a GMP-compliant environment demonstrated a favorable safety profile and high efficacy in treating patients with R/R B-ALL. Larger studies are warranted to confirm these findings.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987734","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":"Modulating PI3K/Akt/mTOR-driven autophagy in liver cancer. The role of phytochemicals.","authors":"Poonam Lal, Jitendra Patel","doi":"10.1007/s00280-026-04949-y","DOIUrl":"https://doi.org/10.1007/s00280-026-04949-y","url":null,"abstract":"<p><p>Hepatocellular carcinoma is one of the major cancer related causes of mortality all over the world that is mainly caused by successive activation of PI3K/Akt/mTOR signalling axis and subsequent regulation of autophagy by the medium. This review analyses the molecular picture of PI3K/Akt/mTOR pathway in liver cancer, such as PTEN, receptor tyrosine kinase, Akt isoform, mTOR complex, GSK 3Β, CREB, FOXO protein, MDM2 p53 axis, NF kB, and lipid metabolic controller. The dual role of autophagy as a tumour suppressive and tumour promoting process is particularly focused on in regard to the therapeutic resistance to agents like sorafenib. The review summarizes preclinical evidence demonstrating that major classes of phytochemicals, including polyphenols, flavonoids, alkaloids, and terpenoids, target key regulatory components of the PI3K/Akt/mTOR mediated autophagy network. These substances regulate the ULK1 activation, AMPK signalling, reactive oxygen species processes and autophagy crosstalk to apoptosis, and hepatocellular carcinoma model metabolic remodelling. The in vitro and in vivo studies done using the mechanism of action reinforce the idea that phytochemicals are multi target regulators that can restore cytoprotective and cytotoxic autophagy. Finally, the existing challenges in translational research, such as pharmacokinetic issues, biomarker voids, tumour heterogeneity, and resistance, are critically evaluated to set priorities of introducing phytochemicals into the liver cancer treatment in a precision-based fashion.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988198","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":"Characterization of DPYD pharmacogenetic variation in Mexican patients with gastrointestinal malignancies.","authors":"Vanessa Gonzalez-Covarrubias, Andrea Morales-Alfaro, Oscar Bonilla-Jimenez, Mauricio Rodríguez-Dorantes, Emmanuel Frías-Jimenez, Enrique Soto-Perez-de-Celis","doi":"10.1007/s00280-026-04955-0","DOIUrl":"https://doi.org/10.1007/s00280-026-04955-0","url":null,"abstract":"<p><strong>Purpose: </strong>Fluoropyrimidines are among the most widely used chemotherapeutic agents for gastrointestinal malignancies, but interindividual variability in dihydropyrimidine dehydrogenase (DPD) activity, encoded by DPYD, can lead to severe or lethal toxicities. Most pharmacogenetic data on DPYD originates from European populations, limiting the applicability of current guidelines in admixed groups.</p><p><strong>Methods: </strong>We evaluated DPYD pharmacogenetic variation and its association with fluoropyrimidine-related adverse events in Mexican patients with gastrointestinal cancers. Adverse events were prospectively assessed using CTCAE v5.0. Genotyping was performed with the Illumina Global Screening Array and analyzed using PLINK and R.</p><p><strong>Results: </strong>A total of 208 patients were enrolled, and 192 samples passed genotyping quality control; 156 patients received fluoropyrimidines. Only three patients (1.5%) carried actionable DPYD variants (rs3918290, rs67376798 and rs75017182), yielding allele frequencies of 0.26%, approximately ten-fold lower than those reported in European cohorts. Genome-wide analyses did not reveal significant genotype-phenotype associations, though suggestive variants in SDK1, ZPBP, and FGF12 were observed. Pharmacodynamic analyses identified frequent variation in TYMS rs2847153 and MTHFR rs1801133, both previously associated with fluoropyrimidine toxicity. Overall, patients exhibited a predominantly Native Mexican ancestry (56.5%), which may explain the markedly low frequency of actionable DPYD alleles commonly found in European populations.</p><p><strong>Conclusions: </strong>These findings highlight the limited representation of admixed populations in pharmacogenetic research and underscore the need for population-specific data to inform safe and equitable fluoropyrimidine dosing.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988217","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":"Combination of PARP inhibitor olaparib and a vascular disrupting agent reduces tumor growth in a preclinical model of prostate cancer.","authors":"Evangelia Sereti, Susan Evans-Axelsson, Jan Törnell, Stefan Rehnmark, Marita Högberg, Anders Bjartell","doi":"10.1007/s00280-026-04946-1","DOIUrl":"10.1007/s00280-026-04946-1","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to characterize the antiproliferative and antitumor activity of NOV202, a novel vascular-disrupting and microtubule-destabilizing compound, alone and in combination withthe PARP inhibitor olaparib, in preclinical prostate cancer models in vitro and in vivo.</p><p><strong>Methods: </strong>DU145 (carrying a BRCA2 variant of unknown significance) and PC-3 (BRCA2 wildtype) prostate cancer cells were implanted in NMRI nude mice. Mice received oral olaparib, NOV202, or both for 21 days. Tumor growth was monitored via bioluminescence imaging and caliper measurements. By immunohistochemistry we assessed DNA damage (γH2AX), homologous recombination repair (RAD51), hypoxia (HIF-1α), proliferation (Ki-67), vascularization (CD31) and apoptosis (cleaved caspase 3). Cell viability assays and western blot analyses were performed to assess treatment-induced DNA-damage and apoptosis markers and to evaluate synergistic effects in vitro.</p><p><strong>Results: </strong>Olaparib and NOV202 independently reduced tumor growth in both xenograft models. NOV202 was the dominant single agent in vivo, and adding olaparib resulted in a modest increase in tumor growth inhibition over NOV202 alone. Immunohistochemistry showed treatment-associated increases in DNA damage and reduced vascularization in tumors. All treatments were well tolerated with minimal signs of toxicity. In vitro, the combination induced synergistic antiproliferative effects. At the protein level, DNA-damage and apoptosis markers were increased mainly by olaparib and were not further enhanced by the combination.</p><p><strong>Conclusion: </strong>NOV202 showed potent single-agent antitumor activity in both prostate cancer xenograft models. The combination with olaparib was synergistic in vitro at low nanomolar NOV202 concentrations but did not provide a clear additional benefit over NOV202 alone in vivo.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988249","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":"Risk factors associated with febrile neutropenia in patients with esophageal cancer receiving 5-fluorouracil plus cisplatin combination chemoradiotherapy.","authors":"Daiki Eto, Ken Shiraiwa, Ryota Tanaka, Takahiro Sumimoto, Ryosuke Tatsuta, Hiroki Itoh","doi":"10.1007/s00280-026-04948-z","DOIUrl":"https://doi.org/10.1007/s00280-026-04948-z","url":null,"abstract":"<p><strong>Purpose: </strong>To identify risk factors for febrile neutropenia (FN) in patients with esophageal cancer receiving the first cycle of definitive chemoradiotherapy with 5-fluorouracil plus cisplatin and concurrent radiotherapy (FP+R therapy).</p><p><strong>Methods: </strong>We conducted a retrospective single-center cohort study of patients who started FP+R at Oita University Hospital between April 2011 and June 2023. The primary outcome was FN onset in cycle 1. Univariate tests and multivariable logistic regression [forced entry: age, C-reactive protein (CRP), prognostic nutritional index (PNI), dysphagia] were used to evaluate association with FN development. Receiver operating characteristic (ROC) analysis was conducted to evaluate the predictive performance of baseline CRP for FN.</p><p><strong>Results: </strong>Among 120 patients studied, grade ≥ 3 neutropenia occurred in 37 (30.8%) and FN in 14 (11.7%) during the first cycle. In multivariable analysis, higher baseline CRP was independently associated with increased FN risk [odds ratio (OR) 1.790; 95% confidence interval (CI) 1.120-2.850; p = 0.014], whereas dysphagia showed a non-significant association (OR 2.890; p = 0.145). Age and PNI were not independent predictors. ROC analysis for baseline CRP yielded area under the ROC curve of 0.699 (95% CI 0.520-0.877; p = 0.021) with optimal cut-off value of 0.68 mg/dL (sensitivity 61.54%; specificity 70.65%).</p><p><strong>Conclusion: </strong>Baseline systemic inflammation, indicated by elevated CRP, is an independent risk factor for FN development during FP+R therapy. Despite the regimen having an intermediate FN risk, patients with elevated pre-treatment CRP may need closer monitoring. This biomarker may help clinicians perform a more comprehensive risk assessment alongside conventional patient-specific factors.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987952","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":"LiCl induces GSK-3β mediated autophagy, DNA damage, and cell cycle arrest in HPV driven cervical cancer cells.","authors":"Arusha Modi, Bishnu Prasad Parida, Satyajit Pradhan, Sunita Singh, Gopeshwar Narayan","doi":"10.1007/s00280-026-04956-z","DOIUrl":"https://doi.org/10.1007/s00280-026-04956-z","url":null,"abstract":"<p><p>High-risk HPV infections induce cervical cancer progression by disrupting cellular homeostasis and survival pathways, including autophagy. Targeting autophagy represents a promising therapeutic strategy. Lithium chloride (LiCl), extensively studied for its neuroprotective properties, can be investigated for its potential anticancer effects in HPV-driven cervical cancer cells. Treatment with 30 mM LiCl induced significant phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9, inducing functional inhibition and downstream signal alterations. This modulation of GSK-3β activity compromised genomic integrity, validated by increased double strand DNA breaks, increased oxidative and cellular stress, and reduced antioxidant enzyme activity. Consequently, LiCl treated cells exhibited significant G₂/M phase arrest, indicating disruption in cell cycle progression. Interestingly, the observed cytotoxicity occurred independently of classical apoptotic pathways, suggesting the activation of alternative cell death mechanisms. Mechanistic studies revealed a robust autophagic flux, with GSK-3β mediated autophagy, validated through siRNA mediated knockdown experiments. These findings highlight a novel cytotoxic mechanism of LiCl and propose its potential repurposing from neurobiology to targeted cancer therapeutics.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954875","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":"Bridging tumor growth dynamics and survival in preclinical oncology drug development - a Tumor Growth Inhibition and Time-to-Event (TGI-TTE) modeling framework.","authors":"Kumar Kulldeep Niloy, Jamie Horn, Nazmul Hasan Bhuiyan, Suhas S Bhosale, Khaled A Shaaban, Thomas E Prisinzano, Jon S Thorson, Jurgen Rohr, Markos Leggas","doi":"10.1007/s00280-026-04947-0","DOIUrl":"10.1007/s00280-026-04947-0","url":null,"abstract":"<p><strong>Purpose: </strong>To develop a tumor growth inhibition and time-to-event (TGI-TTE) modeling framework linking drug exposure, tumor dynamics, and survival. Modeling used preclinical efficacy studies with MTMSA-Trp, a preclinical-stage anti-tumor agent for Ewing sarcoma.</p><p><strong>Methods: </strong>Tumor volume and survival data from Ewing sarcoma mouse xenografts treated with MTMSA-Trp (0.3-2.85 mg/kg) were analyzed. A Simeoni TGI model was used to estimate individual exponential and linear tumor growth rates. A parametric log-logistic TTE model was used to describe mouse survival across treatment groups by incorporating post hoc TGI metrics and regimen-specific average concentrations derived from the PK model as covariates associated with the model-derived event-time distribution. Models were evaluated using the precision of parameter estimates, goodness-of-fit plots, and bootstraps.</p><p><strong>Results: </strong>The TGI model accurately described individual tumor growth dynamics, yielding precise parameter estimates (RSEs < 15%). The final TTE model successfully captured the observed Kaplan-Meier curves across treatment groups (RSEs < 20%). As expected from the endpoint definition, higher regimen-specific average concentration corresponded to longer model-derived survival (coefficient = 0.63), whereas higher exponential and linear tumor growth rates corresponded to shorter model-derived survival (coefficients = - 0.75 and - 0.46, respectively).</p><p><strong>Conclusion: </strong>This framework quantitatively links tumor dynamics, drug exposure, and survival and may support the design, analysis, and simulation-based evaluation of dose regimens in preclinical oncology studies.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954854","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":"Ototoxicity beyond platinum-based derivatives.","authors":"Cecília Vieira Peruch, Marcia Salgado Machado, Vera Beatris Martins, Felipe de Oliveira Goulart, Monalise Costa Batista Berbert, Eliane Dallegrave","doi":"10.1007/s00280-026-04944-3","DOIUrl":"10.1007/s00280-026-04944-3","url":null,"abstract":"<p><strong>Purpose: </strong>Ototoxicity caused by chemotherapy is a growing problem. Literature highlights the effects of platinum compounds. However, other chemotherapy drugs also have demonstrated audiological changes. The objective of this study was to compare pre- and post-treatment distortion product otoacoustic emissions (DPOAEs) in adult patients undergoing different chemotherapy regimens.</p><p><strong>Methods: </strong>Cohort study comprising 174 individuals receiving chemotherapy (CT) between April 2022 and December 2023. DPOAE were evaluated in all patients at 2 kHz, 4 kHz, 6 kHz, 8 kHz, 10 kHz, and 12 kHz, before initiating chemotherapy and after completing the treatment. For differential analysis, the protocols were grouped into CT with platinum-based agents and other protocols.</p><p><strong>Results: </strong>A reduction in response in at least one frequency of the DPOAE test was observed in 79% of the patients. 81% of those who received CT without platinum derivatives exhibited alterations in post-treatment examinations, whereas in the group with platinum-based compounds, alterations were observed in 79% of the subjects. Different percentages of response deterioration were observed across frequencies: 27.6% at 2 kHz, 24.6% at 4 kHz, 41.2% at 6 kHz, 58.8% at 8 kHz, 57.4% at 10 kHz, and 72.4% at 12 kHz. The ototoxic effect of chemotherapy protocols, with and without platinum, was more pronounced at higher frequencies, with no statistically significant difference between the groups.</p><p><strong>Conclusion: </strong>Chemotherapy has shown signs of ototoxicity through changes in DPOAEs in the sample studied. The ototoxic effects were similar between drug protocols with and without platinum, highlighting the need for audiological monitoring in all chemotherapy patients.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917874","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":"Birinapant enhances cisplatin sensitivity in epithelial ovarian cancer through modulation of apoptotic and survival signaling pathways.","authors":"Elham Shahnazi, Arman Rostamlou, Aras Gezer, Aysegul Uysal, Cumhur Gunduz","doi":"10.1007/s00280-026-04938-1","DOIUrl":"https://doi.org/10.1007/s00280-026-04938-1","url":null,"abstract":"<p><strong>Background: </strong>Resistance to platinum-based chemotherapy in epithelial ovarian cancer is frequently driven by dysregulation of apoptotic pathways and overexpression of inhibitor of apoptosis proteins (IAPs). Smac mimetics, such as Birinapant, target IAPs and modulate TNF-α-associated signaling; however, their therapeutic efficacy is highly context-dependent.</p><p><strong>Methods: </strong>We investigated the effects of Birinapant in combination with Cisplatin in ovarian cancer cell lines with distinct sensitivity profiles (SKOV3 and MDAH-2774), along with normal human endometrial stromal cells (HESC) to assess selectivity. Cell viability was measured using the MTT assay, and drug interactions were evaluated using the Chou-Talalay method. Apoptosis was quantified by Annexin V/PI flow cytometry. Protein expression (cIAP1, NF-κB, Caspase-3/8) was analyzed by immunofluorescence, and gene expression (BIRC2, CASP3/8, RELA, TNF) was assessed by RT-qPCR.</p><p><strong>Results: </strong>The Birinapant-Cisplatin combination significantly reduced cell viability in SKOV3 cells and demonstrated strong synergistic effects (CI = 0.057-0.237), accompanied by substantial dose reduction. In contrast, MDAH-2774 cells exhibited limited responsiveness and predominantly antagonistic interactions. Mechanistically, combination treatment in SKOV3 cells was associated with reduced cIAP1 expression, suppression of NF-κB signaling, and activation of Caspase-8 and Caspase-3. Notably, TNF Mrna expression was strongly increased (log₂FC ≈ + 5.6), supporting involvement of TNF-associated apoptotic signaling.</p><p><strong>Conclusion: </strong>Birinapant increased the sensitivity of SKOV3 ovarian cancer cells to cisplatin by enhancing TNF-α-associated apoptotic signaling, while this synergistic effect was not observed in MDAH-2774 cells, emphasizing the importance of cellular context in determining SMAC mimetic responses. Our findings suggest that TNF-α responsiveness, cIAP1 (BIRC2)-related signaling, and the ability of cancer cells to activate apoptotic pathways, particularly caspase-8, may serve as potential biomarkers for identifying tumors more likely to respond to Birinapant-based combination therapies. Further studies using additional ovarian cancer models and clinical samples are required to validate the predictive value of these biomarkers.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911028","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":"Trastuzumab treatment is associated with ferroptosis-related alterations in HER2-positive breast cancer organoids.","authors":"Ming Lei, Zhixiong Li, Chunsong Xiong, Fen Xie, Lingyan Liu, Dan He","doi":"10.1007/s00280-026-04943-4","DOIUrl":"https://doi.org/10.1007/s00280-026-04943-4","url":null,"abstract":"<p><p>Trastuzumab is widely used for HER2-positive breast cancer, but its relationship with ferroptosis remains unclear. In this study, patient-derived breast cancer organoids were used to examine trastuzumab-associated ferroptosis-related changes and the possible involvement of p53 signaling. Three independent HER2-positive breast cancer organoid lines were used for the main functional experiments, and three HER2-low organoid lines were included as control models. The IC50-based working concentration of trastuzumab was 66.31 µg/mL. Transcriptome analysis revealed enrichment of ferroptosis- and p53-related pathways after trastuzumab treatment. In HER2-positive organoids, trastuzumab reduced organoid viability and altered organoid morphology, accompanied by increased MDA, Fe²⁺, and ROS levels and decreased GSH/GSSG, SLC7A11, and GPX4 expression. The same treatment did not produce comparable changes in HER2-low organoids. Fer-1 partially attenuated the changes in organoid viability and ferroptosis-related indicators. PFT-α showed a similar partial rescue effect. In addition, p53 knockdown weakened several trastuzumab-associated changes, including alterations in viability, oxidative stress-related markers, and SLC7A11/GPX4 expression. These findings suggest that trastuzumab treatment is associated with ferroptosis-related biochemical and molecular alterations in HER2-positive breast cancer organoids, and that p53-related signaling may participate in this process.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878792","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}