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.
Docetaxel micellar (DM) is a novel polysorbate-free docetaxel formulation that does not require steroid premedication. The aim of this study was to define the safety, pharmacokinetics (PK) and preliminary activity of DM in patients with metastatic castration-resistant prostate cancer (mCRPC). DM was administered intravenously to chemotherapy-naïve patients with mCRPC every 3 weeks following a 3 + 3 design (75, 90, 100 mg/m2) until disease progression or unacceptable toxicity (maximum 10 cycles). A total of 11 patients were recruited from June 2021 to April 2023. No dose limiting toxicities (DLT) were observed at 75 or 90 mg/m2. Two out of 5 patients experienced DLT at 100 mg/m2 (grade 4 neutropenia ≥ 7 days and grade 2 nausea/fatigue/diarrhoea requiring dose reduction at cycle 2, respectively). Most frequent all-grades TRAE included fatigue (91
CUB domain-containing protein 1 (CDCP1) is an emerging tumor-associated surface antigen broadly expressed in solid tumors and linked to poor prognosis, making it an attractive target for selective therapeutic delivery. We evaluated CDCP1 as a platform for two distinct therapeutic modalities: an antibody-drug conjugate (ADC) for cytotoxic payload delivery and an immunocytokine for targeted delivery of interferon-α2b (IFNα2b). Novel humanized anti-CDCP1 monoclonal antibodies were generated and characterized for binding to recombinant and cell-surface CDCP1. CDCP1 expression in tumor cells and xenografts was assessed by flow cytometry and immunohistochemistry. CDCP1-targeted ADCs and CDCP1-targeted IFNα2b fusion proteins, including attenuated IFNα2b variants, were evaluated for in vitro cytotoxicity and in vivo antitumor activity in multiple solid tumor xenograft models. A murine cross-reactive anti-CDCP1 ADC was further assessed in an acute mouse toxicity study. CDCP1 was broadly expressed across multiple solid tumor cell lines and xenografts. CDCP1-targeted ADCs mediated potent, target-dependent cytotoxicity in vitro, and MMAE-conjugated ADCs showed robust antitumor activity in pancreatic, lung, breast, and colon xenograft models, with tumor growth inhibition up to 90
Localized intra-arterial delivery of gemcitabine (IAG) may provide advantages in terms of increased tissue concentration and decreased systemic dosing. We hypothesized IAG may result in decreased systemic gemcitabine concentration and associated side effects due to intracellular delivery prior to conversion to gemcitabine’s inactive metabolite, difluorodeoxyuridine (dFdU). Here we report the results of a pharmacokinetics and pharmacodynamics sub-study within the TIGeR-PaC phase 3 clinical trial (NCT03257033). Analyses were performed for 16 participants across 6 TIGeR-PaC study sites; 11 participants received localized IAG and 5 participants received systemic intravenous gemcitabine (IVG). Gemcitabine and dFdU assays were performed on blood samples collected immediately before, during, and after infusion. CA 19 − 9 levels were measured prior to and 2 weeks after IAG treatment. Maximum plasma drug concentration (Cmax) and the area under the drug plasma concentration curve (AUC0−t) were compared between treatment groups. Pearson’s correlation for AUC0−t and the percent change in CA 19 − 9 levels was calculated for the IAG group. IAG resulted in lower gemcitabine Cmax and AUC0−t and higher dFdU Cmax and AUC0−t compared to IVG, consistent with a more rapid conversion of gemcitabine to dFdU with IAG versus IVG. With IAG, there was a significant correlation between increased dFdU levels and a pre- to post-treatment reduction in CA 19 − 9 levels (Pearson’s r = -0.75; P = 0.034). In addition to providing increased local potency, localized IAG, in which gemcitabine is rapidly converted to its inactive metabolite dFdU, may also be beneficial in decreasing gemcitabine-related systemic side effects.
Selpercatinib is a selective RET inhibitor with established efficacy in RET-altered malignancies; however, data regarding its long-term safety and pharmacokinetic behavior remain limited. We report a case of fatal hepatic failure occurring during prolonged selpercatinib therapy and describe associated clinical and pharmacokinetic findings. A 78-year-old man with RET-mutant medullary thyroid carcinoma received selpercatinib (160 mg twice daily) as second-line therapy following disease progression during vandetanib treatment. After dose interruption and subsequent dose adjustments, the patient achieved a sustained partial response during long-term treatment. Approximately 27 months after selpercatinib initiation, he developed progressive dyspnea, pleural effusion, and severe hepatic dysfunction, ultimately resulting in death. Plasma selpercatinib concentrations were measured during stable disease and later during hepatic decompensation. Pharmacokinetic analysis indicated that drug exposure during the stable treatment period was within the anticipated range, suggesting that elevated drug concentrations observed at the time of hepatic decompensation represented a consequence of impaired clearance rather than a primary cause. These findings implicate circulatory compromise as a potential mediating mechanism and highlight the importance of cardiovascular as well as hepatic monitoring during prolonged selpercatinib therapy. This case highlights a potential indirect mechanism of severe hepatic failure during long-term selpercatinib therapy, in which circulatory compromise—potentially mediated by selpercatinib-associated cardiovascular effects—may have contributed to congestive hepatic decompensation rather than direct drug-induced hepatotoxicity. These findings underscore the importance of integrating cardiovascular surveillance with hepatic monitoring during prolonged selpercatinib treatment.
Vepdegestrant is an investigational, orally administered PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader being evaluated for the treatment of ER+/HER2- advanced breast cancer, with promising results in prior studies of Western and Japanese patients. Vepdegestrant had not been previously evaluated in Chinese patients. This phase 1 study (NCT05732428) assessed pharmacokinetics (PK) of vepdegestrant and its epimer (ARV-473), and safety and preliminary efficacy of vepdegestrant monotherapy (200 mg once daily [QD] in 28-day cycles) in Chinese adults with ER+/HER2- advanced breast cancer who had received ≥ 1 prior line of endocrine therapy. Nine female Chinese patients were treated (median age, 56.0 [range: 42.0–69.0] years; six received ≥ 3 prior anticancer therapies in the advanced setting). Geometric mean area under the plasma concentration–time curve over the dosing interval was 9575 ng*h/mL following a single dose and 18,340 ng*h/mL following multiple daily doses on day 15; maximum observed concentration of vepdegestrant was 633.2 ng/mL and 1035 ng/mL after single and multiple doses, respectively. Vepdegestrant was well tolerated. Most treatment-related adverse events (TRAEs) were grade 1 or 2. Two patients experienced grade 3 TRAEs; no patients discontinued due to AEs. Objective response and clinical benefit rates were 33.3
Sorafenib remains a systemic treatment option for advanced hepatocellular carcinoma (HCC), but its clinical efficacy is limited by rapid development of adaptive cellular responses that promote cell survival and phenotypic plasticity. Store-operated calcium entry (SOCE) is a key regulator of intracellular calcium signaling and has been implicated in proliferation, apoptosis, migration, and epithelial–mesenchymal plasticity in cancer. This study investigated the association between SOCE and early adaptive responses to sorafenib in Huh7 HCC cells. Huh7 cells were treated with sorafenib, the SOCE inhibitor SKF-96365, or their combination. Functional effects were evaluated using real-time proliferation assays, intracellular calcium measurements, apoptosis analysis, and wound-healing assays. Findings were complemented by integrated bioinformatic analyses of TCGA-LIHC and related HCC datasets. Sorafenib treatment significantly enhanced calcium influx following endoplasmic reticulum calcium depletion, consistent with activation of SOCE as part of an adaptive response. Pharmacological inhibition of SOCE markedly attenuated this calcium influx and suppressed cell proliferation. Combined treatment enhanced sorafenib-induced apoptosis and reduced wound closure, accompanied by decreased expression of mesenchymal markers and increased E-cadherin levels, consistent with a shift toward a more epithelial phenotype. Integrated bioinformatic analyses revealed an association between TRPC6-related signaling and epithelial–mesenchymal plasticity, as well as subtype-specific expression patterns linked to aggressive tumour behavior in human HCC datasets. These findings suggest that SOCE is associated with early adaptive responses to sorafenib in Huh7 cells, and that its pharmacological inhibition may enhance sorafenib-induced antitumor effects. Given the reliance on a single cell line and a non-selective pharmacological inhibitor, these findings should be considered hypothesis-generating, and further validation using additional HCC models and genetic approaches is warranted.
Cetuximab sarotalocan is an innovative photoimmunotherapy agent for cancer treatment, with an unclear safety profile. We analysed the clinical adverse event profile of cetuximab sarotalocan in photoimmunotherapy. In this retrospective study, we analysed real-world clinical data of patients with head and neck cancer from the Japanese Adverse Drug Event Report database. Patient demographics, as well as the nature of adverse events and their outcomes and co-occurrences, were analysed. Cetuximab sarotalocan adverse event reports (n = 227) predominantly included older male patients. The most frequent adverse event was laryngeal oedema, followed by upper respiratory and oral complications. Recovery rates were high for laryngeal oedema and tongue-related adverse events but poor for fistula-related complications. Co-occurrence was found between different adverse events, particularly laryngeal oedema and dysphagia. The described safety profile of cetuximab sarotalocan in photoimmunotherapy offers insights for its proper use as well as baseline data for the development and improvement of cancer photoimmunotherapy.
Safety evaluation in first-in-human (FIH) Phase 1 oncology trials is largely descriptive and provides limited quantitative insights. This study characterized the dynamics of platelet count (PLT) and alanine aminotransferase (ALT) concentration in the LP-184 FIH study and explored statistical modeling to support personalized dosing strategies. PLT and ALT data were analyzed to characterize temporal trends, inter-patient variability, and correlations with baseline characteristics and exposure. Firth logistic regression was fitted to identify potential contributors to clinically relevant PLT abnormalities. PLT nadir predominantly occurred in cycle 2, with baseline PLT and total single-infusion dose as critical contributors. Patients with baseline PLT below 200 K/µL were at high risk of developing grade ≥ 2 PLT decreased adverse events. ALT levels mostly peaked in cycle 1, with a moderate association with dose and no evident relationship to baseline liver metastases. Patients with glioblastoma exhibited a higher probability of experiencing ALT increased events at grade ≥ 2. A single infusion dose above 40 mg was associated with increased occurrence of high-grade PLT decreased and ALT increased events. A personalized dose recommendation strategy is proposed. Integration of in-depth data analytics in FIH studies facilitates earlier safety signal detection and informs safety monitoring and dose selection in later studies. ClinicalTrials.gov, TRN: NCT05933265, Registration date: 23 June 2023.
Breast cancer is the leading cause of cancer-related death in women worldwide. There is increasing interest in using detailed body composition parameters, such as skeletal muscle mass and adiposity, to better predict treatment response, toxicity, and survival in breast cancer patients receiving neoadjuvant chemotherapy (NAC). This study synthesised current literature on the effect of body composition in breast cancer patients undergoing NAC and identified gaps for future research. A scoping review was conducted in accordance with PRISMA-ScR and Arksey O’Malley frameworks. Embase, MEDLINE, PubMed, and Google Scholar were searched for studies published between 2010 and 2025 to map available evidence. Eligible studies included female breast cancer patients receiving NAC with body composition assessment and at least one outcome of response, toxicity, or prognosis. Twenty studies met inclusion criteria. Computed tomography at the L3 vertebral level was the most common assessment method. Findings were heterogeneous; 3 studies reported a statistically significant association between sarcopenia and reduced pathological response, while results for adiposity were inconsistent. Half of the studies assessing toxicity reported higher toxicity rates in patients with sarcopenia and/or adiposity. Prognostic findings were variable, with some studies reporting associations with visceral adiposity, and only one study reporting a significant association with sarcopenia. Evidence regarding the relationship between adiposity and NAC toxicity and prognosis in breast cancer remains suggestive, while findings for sarcopenia are inconsistent. Prospective, standardised studies are needed to clarify the role of body composition in breast cancer outcomes and its relevance in treatment planning.
Oxaliplatin resistance remains a major obstacle in the treatment of colorectal cancer (CRC). This study aimed to determine whether MYC contributes to oxaliplatin resistance by regulating ferroptosis and to clarify the downstream mechanisms involving FTH1 and GPX4. Parental CRC cell lines, including HCT116, HT-29 and SW480, together with oxaliplatin-resistant HCT116-R cells, were used. MYC expression was manipulated by knockdown or overexpression. Oxaliplatin sensitivity was evaluated using CCK-8 assays and IC50 analysis. Intracellular Fe2⁺ and reactive oxygen species (ROS) levels were measured to assess ferroptosis-associated changes. RT-qPCR and western blotting were performed to examine gene and protein expression. Chromatin immunoprecipitation-qPCR and dual-luciferase reporter assays were used to investigate the transcriptional regulation of FTH1 and GPX4 by MYC. Rescue experiments with FTH1 or GPX4 overexpression and sorafenib treatment were also conducted. MYC knockdown significantly increased oxaliplatin sensitivity in both parental and resistant CRC cells and elevated intracellular Fe2⁺ and ROS levels. MYC directly bound to the promoter regions of FTH1 and GPX4 and enhanced their transcriptional activity. Downregulation of MYC reduced FTH1 and GPX4 expression, whereas re-expression of either FTH1 or GPX4 partially restored oxaliplatin resistance. Sorafenib further enhanced oxaliplatin sensitivity in resistant cells. MYC promotes oxaliplatin resistance in CRC cells, at least in part, by transcriptionally upregulating FTH1 and GPX4 and suppressing ferroptosis-associated cell death. The MYC–FTH1/GPX4–ferroptosis axis may represent a potential therapeutic target for overcoming oxaliplatin resistance in CRC.
Dihydropyrimidine dehydrogenase (DPD), which is encoded by the DPYD gene, plays an important role in the metabolism of fluoropyrimidine (FP) drugs, including tegafur, in S-1. A decrease in DPD activity can cause severe FP-related toxicity. The Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for FP and DPYD polymorphisms recommend FP dose adjustments based on the four major DPYD polymorphisms. However, multiple rare variants of DPYD have been reported. We present the case of a man in his 50s with cT3N0M0 tongue squamous cell carcinoma who developed severe myelosuppression and diarrhea after the initiation of S-1 (tegafur/gimeracil/oteracil) despite appropriate dosing. On day 20 of treatment, the patient developed grade 4 neutropenia and septic shock and required ICU admission. Genetic testing identified a rare heterozygous DPYD variant (c. 812delT) that causes a frameshift and a presumed loss of enzyme function, suggesting an underlying cause of the severe adverse events. Although severe toxicity occurred, marked tumor shrinkage allowed for less invasive surgery. This case highlights the need for expanded genetic screening beyond the guideline-listed variants, particularly in Asian populations, where common variants differ. Combining genotypic and phenotypic evaluations of DPD activity may improve the prediction and prevention of FP-related toxicities, supporting safer and more effective use of FP drugs.
Currently, no established guidelines exist for dosing chemotherapy or immunotherapy in patients with achondroplasia. A 69-year old female with congenital achondroplasia was diagnosed with stage IV non-small cell lung carcinoma type adenocarcinoma, with high Tumor Mutational Burden and 20
Renal cell carcinoma (RCC) is a highly vascularized and metastatic malignancy of the kidney. The 5-year overall survival rate of RCC patients remains poor despite the development of therapeutic modalities. Therefore, identifying novel approaches to increase the sensitivity of RCC cells to drugs could help prolong patient survival. Recently, Drug repurposing, which leverages the established safety profiles and pharmacological properties of existing medications, has emerged as a promising alternative to traditional drug development. This approach can accelerate the translation of new therapies into clinical practice and is often associated with lower attrition rates in clinical trials. Recent evidence supports the therapeutic potential of various repurposed drugs against RCC. This review article summarizes and shows the effectiveness and potential of repurposed drugs including metabolic and cardiovascular modulators (metformin, simvastatin), antimicrobial and antiparasitic agents (artesunate, ivermectin, ketoconazole, chloroquine, hydroxychloroquine, niclosamide, doxycycline, pentamidine), mTOR inhibitors (temsirolimus, everolimus, rapamycin), anti-inflammatory and analgesic agents (aspirin, celecoxib), and agents with other mechanisms of action (acetazolamide, disulfiram). These agents exert their anticancer effects against RCC by modulating multiple signaling pathways, including PI3K/AKT/mTOR, AMPK, JAK2/STAT3, ERK1/2, Wnt/β-catenin, and RhoA/ROCK, as well as by inducing autophagy inhibition, ferroptosis, oxidative stress, and mitochondrial dysfunction, highlighting their utility in RCC therapy and emphasizing their clinical relevance.
Zolbetuximab plus chemotherapy is standard first-line therapy for HER2-negative, CLDN18.2-positive advanced gastric or gastroesophageal junction cancer (GC/GEJC), but the incidence, course, and clinical correlations of zolbetuximab-related gastric mucosal injury and hypoalbuminemia remain unclear. We thus evaluated these relationships and the clinical course in real-world practice. We retrospectively analyzed 38 patients with HER2-negative, CLDN18.2-positive, advanced GC/GEJC treated with zolbetuximab plus chemotherapy at a single center. Associations between endoscopic findings and albumin changes from baseline were analyzed. Median albumin decreased from 3.7 to 2.6 g/dL. The median albumin decline was greater in patients without gastrectomy (− 1.0 g/dL) or with partial gastrectomy (− 1.1 g/dL) than in those with total gastrectomy (− 0.3 g/dL; P = 0.009 and 0.007). Albumin levels fell rapidly at weeks 1–3 and recovered toward baseline by weeks 19–27. Upper gastrointestinal endoscopies were performed in patients with a remaining stomach, showing peak abnormalities within 7–12 weeks; no cases with grade ≥ 2 gastric mucosal injury were observed after week 25. White exudate was associated with albumin decline (− 0.9 vs. −0.4 g/dL, P = 0.023). The presence of white exudate demonstrated a significant association with a marked decrease in serum albumin levels. The risk of hypoalbuminemia appeared to be lower in patients after total gastrectomy. Serum albumin levels decreased after treatment initiation and subsequently showed a tendency to recover over time. Gastric mucosal abnormalities were most frequently observed during the early phase of treatment and were less common in examinations performed after week 25.
Protein kinase inhibitor (PKI) therapy increasingly relies on personalized approaches such as therapeutic drug monitoring and pharmacogenetic testing. Understanding PKI metabolism is essential for these methods to be effective, notably for determining the substance to be quantified and the enzyme for which the genotypic metabolizer status needs to be predicted. For most drugs, however, human in vivo metabolite profiles are derived from the mass balance studies conducted by drug developers, typically in small and homogeneous populations. We studied mass balance study characteristics for PKIs, assessing number of participants, sex, and health state, as well as dosing regimen, study location, study duration, and consideration of genetic variation in metabolic enzymes and transporters. Data were primarily extracted from European Public Assessment Reports, supplemented with information from the Drugs@FDA database, ClinicalTrials.gov, and peer-reviewed mass balance study publications. Mass balance studies were conducted for 68 out of the 69 PKIs listed as “authorized” human drugs in the European Medicines Agency database on July 7, 2025 (updated April 18, 2026; +3 PKIs). The studies included 2–12 participants (median = 6), with 90
For decades, oncology dose selection has been guided by the maximum tolerated dose (MTD) and plasma pharmacokinetics (PK), reflecting assumptions appropriate for classical cytotoxic chemotherapies. However, the advent of high-affinity, targeted therapies, including kinase inhibitors, epigenetic modulators, and radioligands challenges this paradigm. These agents achieve robust target engagement at doses far below the MTD, and systemic plasma concentrations often fail to reflect pharmacologically relevant exposure at tumor or hematologic sites. Physiologically-based pharmacokinetic (PBPK) modeling, extended to incorporate target-site dynamics, offers a mechanistic framework linking dose, systemic exposure, and local pharmacology. By integrating tissue physiology, drug properties, and target interactions, target-site PBPK provides insights into heterogeneous tumor penetration, intracellular distribution, and variable target occupancy that plasma PK alone cannot capture. Clinical examples, such as PSMA-targeted radioligands and tyrosine kinase inhibitors, illustrate how these models can inform rational dose selection, optimize ligand design, and guide individualized therapy. As oncology moves toward mechanism-driven, biology-aligned development, target-site PBPK represents a pivotal tool for translating preclinical insights into patient-specific dosing strategies and for redefining the standard of precision pharmacology.
Dexamethasone is routinely used as premedication during weekly paclitaxel to prevent hypersensitivity reactions; however, prolonged corticosteroid exposure may induce clinically relevant metabolic, endocrine, and patient-reported adverse effects. This study evaluated whether selective omission of dexamethasone after the second paclitaxel infusion is safe and explored its effects on quality of life, metabolic/endocrine parameters, and short-term oncologic outcomes, including recurrence and disease-related mortality. In this prospective, randomized, open-label phase III trial, 86 women with stage I–III breast cancer receiving neoadjuvant or adjuvant AC-T or AC-TH chemotherapy were randomized 1:1 to standard dexamethasone premedication or omission after the second weekly paclitaxel infusion. The primary endpoint was safety, defined by hypersensitivity reactions and adverse events. Secondary and exploratory endpoints included patient-reported quality of life using the EORTC QLQ-C30, metabolic and endocrine parameters, and short-term oncologic outcomes. Longitudinal changes were analyzed using generalized estimating equations. Eighty-four patients were included in the final analysis. No hypersensitivity reactions occurred after dexamethasone omission, and treatment completion rates were comparable between groups. After a median follow-up of 3.15 years, recurrence and disease-related mortality were similar between groups in descriptive analyses. The omission strategy was associated with improvements in role functioning and reduced worsening of pain (p = 0.02), constipation (p = 0.01), and nausea/vomiting (p = 0.03). No statistically significant differences were observed for emotional or physical functioning. Endocrine analyses demonstrated reduced IGF-1 levels and a trend toward lower insulin levels. These secondary analyses should be interpreted as exploratory. Selective omission of dexamethasone after the second weekly paclitaxel infusion was safe and well tolerated in this randomized trial. The findings support the feasibility of a corticosteroid-sparing strategy during weekly paclitaxel and suggest potential benefits in selected patient-reported and endocrine outcomes, which warrant confirmation in larger studies. NCT04350229, registered on 16 April 2020.
Osimertinib (OSM), a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, causes skin disorders, such as hand-foot syndrome (HFS), which impairs skin barrier function. Stratum corneum (SC) lipids play an important role in skin barrier function. This study aimed to compare the SC lipid composition and structure of healthy participants with those of patients with OSM-induced HFS. Overall, 47 patients with non-small cell lung cancer were enrolled in this study. All patients received 80 mg/day OSM orally and completed the 56-day prospective observation period. SC samples were obtained from seven patients with OSM-induced HFS (OSC). SC lipid composition (ceramide [CER] and free fatty acids [FFAs]) and structure were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and synchrotron X-ray diffraction, respectively. In healthy SC (HSC), the lipids formed two lamellar phases. Hexagonal and orthorhombic hydrocarbon chain packing was observed in the lateral lipid organization. However, in the OSC, these structures almost disappeared. UPLC-MS/MS analysis revealed that the composition of CER and FFA differed between OSC and HSC and that the carbon chain length of SC lipid components in OSCs was lower compared with that in HSCs. However, no significant differences were observed in the CER levels of the esterified ω-hydroxy fatty acid class, which is involved in the formation of long-period lamellar structures, between the two groups. OSM induces changes in SC lipid structure due to changes in SC lipid composition and a decrease in carbon chain length in OSCs, resulting in impaired barrier function.
