Purpose: Patient-derived cells (PDCs) and patient-derived organoids (PDOs) are complementary preclinical models widely used in translational cancer research. However, their molecular and functional differences have not been systematically characterized. This study established and analyzed paired PDC and PDO models derived from the same gastric cancer ascites to delineate platform-dependent molecular and functional profiles. Materials and Methods: Malignant ascites or pleural fluid obtained from 6 patients with advanced gastric cancer were used to establish paired PDC and PDO models. All pairs underwent comprehensive multi-omics profiling, integrating genomic, transcriptomic, and proteomic data. Phenotypic characterization included morphological, histological, proliferative, and cell cycle analyses. Drug sensitivity assays were performed using 4 chemotherapeutic agents commonly used to treat gastric cancer. Results: The 6 paired PDC and PDO models exhibited distinct morphological characteristics.Whole-genome analyses demonstrated high concordance among primary tumors, PDCs, and PDOs, confirming tumor representation across platforms. Multi-omics profiling identified platform-dependent molecular signatures; PDOs were enriched for extracellular matrix remodeling and stemness, whereas PDCs displayed proliferation- and immune-related signatures. Clinically relevant biomarkers, including HER2 and MET alterations, were concordant with primary tumors. Notably, drug responses differed between platforms and patients, indicating platform-dependent and patient-specific chemosensitivity. Conclusions Paired PDC and PDO models derived from the same patients preserved core patient-specific tumor characteristics while exhibiting distinct molecular and functional profiles. These findings underscore the culture platform as a critical determinant of experimental outcomes and therapeutic responses. Therefore, careful selection of an appropriate preclinical model is essential to accurately address biological questions and optimize precision oncology strategies.

Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Objective: We conducted this study to assess the efficacy and safety of taltirelin hydrate (TH) in patients with ataxia due to spinocerebellar degeneration (SCD). Methods: Patients were randomly assigned to either the taltirelin group (5 mg orally, twice daily) or the control group. The primary endpoint was the change in the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) score at 24 weeks. The secondary endpoints included changes in the K-SARA score at 4 and 12 weeks as well as the Clinical Global Impression Scale, the five-level version of the EuroQol five-dimensional questionnaire, the Tinetti balance test, and gait analysis at 4, 12, and 24 weeks. Results: A total of 149 patients (hereditary:nonhereditary=86:63) were enrolled. There were significant differences in the change in the K-SARA score at 24 weeks from baseline between the taltirelin group and the control group (-0.51±2.79 versus 0.36±2.62, respectively; p=0.0321). For the K-SARA items, the taltirelin group had significantly lower “Stance” and “Speech disturbance” subscores than the control group (-0.04±0.89 versus 0.23±0.79 and -0.07±0.74 versus 0.18±0.67; p=0.0270 and 0.0130, respectively). However, there were no significant differences in changes in other secondary efficacy outcome measures at 24 weeks from baseline between the two treatment arms (p>0.05). Conclusion Clinicians might consider the use of TH in the treatment of patients with ataxia due to SCD.

Objective: We conducted this study to assess the efficacy and safety of taltirelin hydrate (TH) in patients with ataxia due to spinocerebellar degeneration (SCD). Methods: Patients were randomly assigned to either the taltirelin group (5 mg orally, twice daily) or the control group. The primary endpoint was the change in the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) score at 24 weeks. The secondary endpoints included changes in the K-SARA score at 4 and 12 weeks as well as the Clinical Global Impression Scale, the five-level version of the EuroQol five-dimensional questionnaire, the Tinetti balance test, and gait analysis at 4, 12, and 24 weeks. Results: A total of 149 patients (hereditary:nonhereditary=86:63) were enrolled. There were significant differences in the change in the K-SARA score at 24 weeks from baseline between the taltirelin group and the control group (-0.51±2.79 versus 0.36±2.62, respectively; p=0.0321). For the K-SARA items, the taltirelin group had significantly lower “Stance” and “Speech disturbance” subscores than the control group (-0.04±0.89 versus 0.23±0.79 and -0.07±0.74 versus 0.18±0.67; p=0.0270 and 0.0130, respectively). However, there were no significant differences in changes in other secondary efficacy outcome measures at 24 weeks from baseline between the two treatment arms (p>0.05). Conclusion Clinicians might consider the use of TH in the treatment of patients with ataxia due to SCD.

Objective: We conducted this study to assess the efficacy and safety of taltirelin hydrate (TH) in patients with ataxia due to spinocerebellar degeneration (SCD). Methods: Patients were randomly assigned to either the taltirelin group (5 mg orally, twice daily) or the control group. The primary endpoint was the change in the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) score at 24 weeks. The secondary endpoints included changes in the K-SARA score at 4 and 12 weeks as well as the Clinical Global Impression Scale, the five-level version of the EuroQol five-dimensional questionnaire, the Tinetti balance test, and gait analysis at 4, 12, and 24 weeks. Results: A total of 149 patients (hereditary:nonhereditary=86:63) were enrolled. There were significant differences in the change in the K-SARA score at 24 weeks from baseline between the taltirelin group and the control group (-0.51±2.79 versus 0.36±2.62, respectively; p=0.0321). For the K-SARA items, the taltirelin group had significantly lower “Stance” and “Speech disturbance” subscores than the control group (-0.04±0.89 versus 0.23±0.79 and -0.07±0.74 versus 0.18±0.67; p=0.0270 and 0.0130, respectively). However, there were no significant differences in changes in other secondary efficacy outcome measures at 24 weeks from baseline between the two treatment arms (p>0.05). Conclusion Clinicians might consider the use of TH in the treatment of patients with ataxia due to SCD.

Purpose: We evaluated the short-term efficacy and safety of hyaluronic acid (HA) eye drops over a 1-month observational period in patients treated with different HA concentrations for dry eye disease. Methods: This prospective, non-interventional, multicenter observational study included patients aged ≥ 19 years who were diagnosed with dry eye at participating medical institutions and treated with HA eye drops (Xenobella SD; ChongKunDang Pharm., Seoul, Korea). In total, 886 eyes from 886 patients were analyzed. Efficacy was evaluated by changes in tear film break-up time (TBUT), ocular surface staining score, dry eye severity, ocular discomfort scale, and the Ocular Surface Disease Index (OSDI) from baseline to 1 month after treatment. Subgroup analyses were conducted to assess efficacy according to age, contact lens use, and HA concentration. Safety was evaluated using a questionnaire on adverse events. Results: After 1 month of treatment, all dry eye parameters―ocular surface staining score, TBUT, ocular discomfort scale, OSDI, and dry eye severity―improved significantly. Subgroup analyses revealed greater improvement in selected parameters, including TBUT, among patients <60 years, contact lens users, and those treated with higher concentrations of HA (0.18% or 0.3%), compared to patients aged ≥60 years, non–contact lens users, and those receiving the lower concentration of HA (0.1%). Only five mild adverse events were reported. Conclusions This 1-month observational study demonstrated that HA eye drops significantly improved both signs and symptoms of dry eye with minimal adverse events. Therapeutic benefits were more pronounced in younger patients, contact lens users, and those treated with higher HA concentrations (≥0.18%).

Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.