1.DNA Damage and Nuclear Anaplasia Induced by Trastuzumab Deruxtecan in Cancer Cells with Variable HER2 Expression and Homologous Recombination Deficiency Status
So Hyeon KIM ; Yoonjung PARK ; Ahrum MIN ; Hye Yeon PARK ; Yu-Jin KIM ; Sujin HAM ; Jiwon KOH ; Seongyeong KIM ; Dae-Won LEE ; Han Suk RYU ; Jin-Soo KIM ; Kyung-Hun LEE ; Seock-Ah IM
Cancer Research and Treatment 2026;58(2):407-422
Purpose:
Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models.
Materials and Methods:
Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells.
Results:
T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed.
Conclusion
These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.
2.Novel Bronchoscopy Method for Molecular Profiling of Lung Cancer: Targeted Washing Technique
Mi-Hyun KIM ; Hayoung SEONG ; Hyojin JANG ; Saerom KIM ; Wanho YOO ; Soo Han KIM ; Jeongha MOK ; Kwangha LEE ; Ki Uk KIM ; Min Ki LEE ; Jung Seop EOM
Cancer Research and Treatment 2026;58(1):107-114
Purpose:
There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the epidermal growth factor receptor (EGFR) mutation.
Materials and Methods:
A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue.
Results:
In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22.0%, 9.8%, and 29.3%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 36.6%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 82.9% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation.
Conclusion
We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.
3.Cost-Effectiveness Analysis of Daratumumab Monotherapy and Subsequent Therapies in Heavily Treated Relapsed/Refractory Multiple Myeloma: A Feasible Methodology using a Korean Nationwide Population Cohort
Sung-Soo PARK ; Suein CHOI ; Seungpil JUNG ; Seunghoon HAN ; Chaehyeon LEE ; Jinseon HAN ; Soyoung KIM ; Kihyun KIM ; Chang-Ki MIN
Cancer Research and Treatment 2026;58(1):300-310
Purpose:
High-cost novel therapies for multiple myeloma (MM) require evaluation of efficacy and cost-effectiveness.
Materials and Methods:
This study developed a methodology to assess cost-effectiveness using nationwide data from 11,450 newly diagnosed MM patients. A novel algorithm was applied to identify lines of therapy (LoT).
Results:
The number of newly diagnosed MM patients increased significantly, from 873 in 2010 to 1,464 in 2019 (p < 0.001). Advancing LoT was associated with shorter time to next treatment (TTNT) and overall survival (OS) (p < 0.001), while all-cause medical costs increased with each LoT (p < 0.001). Bortezomib-melphalan-prednisolone was the most common frontline regimen for transplant-ineligible patients (29.2%), while bortezomib-thalidomide-dexamethasone was most used for transplant-eligible patients (11.3%). Daratumumab monotherapy demonstrated superior second TTNT (7.8 vs. 5.2 months) and OS (8.5 vs. 5.3 months) compared to standard care in heavily treated MM patients, with statistical significance maintained after cost adjustment. For subsequent therapies following daratumumab, a methodology was developed to estimate required medical costs using the incremental cost-effectiveness ratio (ICER): Expected cost ($)=ICER×(Expected life expectancy–0.567)+35,601.
Conclusion
This study provides a novel cost-effectiveness framework linking treatment efficacy and real-world costs, supporting predictions of societal costs for future MM therapies.
4.Clinical Application of Pharmacogenomics in Stroke Management: Current Evidence and Future Directions
Keon-Joo LEE ; Minkyung KANG ; Eung Joon LEE ; Jaeseong OH ; Na-Young HAN ; Jeong-Yoon LEE ; Joo-Yeon LEE ; Soo Ji LEE ; Stéphanie DEBETTE ; Guillaume PARÉ ; Daniel WOO ; Andrew ELDEIRY ; Young Seo KIM ; Jinkwon KIM ; Jong-Moo PARK ; Juneyoung LEE ; Joohon SUNG ; Jay Chol CHOI ; Hee-Joon BAE
Journal of Stroke 2026;28(1):58-75
Pharmacogenomic variations may significantly influence responses to commonly prescribed stroke medications. Despite accumulating evidence, genetic testing has not yet been widely integrated into stroke care. This review summarizes current evidence and provides practical guidance for clinical implementation. Pharmacogenomic studies and clinical guidelines related to antiplatelet agents, anticoagulants, and statins were reviewed, with particular emphasis on East Asian populations. Substantial evidence supports genotype-guided use of clopidogrel (CYP2C19), warfarin (CYP2C9, VKORC1, CYP4F2), and statins (SLCO1B1, ABCG2). For aspirin, PTGS1/2 and PEAR1 variants have been investigated; however, current data remain insufficient for clinical application. Regarding direct oral anticoagulants (DOACs), candidate genes such as ABCB1 and CES1 demonstrate pharmacokinetic associations, though robust clinical outcome data are lacking. Distinct allele frequencies in East Asians—such as higher prevalence of CYP2C19 and ABCG2 variants—underscore the need for population-specific strategies. Beyond single-gene approaches, polygenic risk scores, pharmacogenomic panels, and integration with multi-omics data and artificial intelligence represent promising directions for personalized therapy. Pharmacogenomic testing can enhance stroke pharmacotherapy, particularly in populations with high frequencies of actionable variants. Broader implementation requires rapid testing platforms, clinician education, tailored clinical guidelines, and real-world validation of aspirin, DOACs, and multi-gene approaches. Future research should expand population-specific studies and integrate pharmacogenomics within the broader framework of precision medicine to ensure equitable clinical benefit.
5.Korean colorectal cancer screening guidelines for asymptomatic, average-risk adults: the 2025 revision
EunKyo KANG ; Jae Myung CHA ; Seo Young KANG ; Kiheon LEE ; Su Young KIM ; Younghoon KIM ; An Na SEO ; Hyo-Jin KANG ; Jong Keon JANG ; Kwang-Pil KO ; Aesun SHIN ; Dae Kyung SOHN ; Youngki HONG ; Eun-Jung CHO ; Minje HAN ; Soo Young KIM ; Hyeon Ji LEE ; Chang Kyun CHOI ; Mina SUH
Journal of the Korean Medical Association 2026;69(3):268-280
Purpose:
To develop the 2025 update to the Korean colorectal cancer (CRC) screening guidelines by systematically evaluating recent evidence, integrating domestic data, and addressing changes since the 2015 guideline revision, thereby providing an evidence-based standard for clinicians and policymakers.
Methods:
A multidisciplinary committee developed the guidelines using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The process included formulation of three key questions addressing screening efficacy, diagnostic accuracy, and optimal screening age and interval. A systematic review of international guidelines and primary literature was conducted, yielding 327 eligible studies. In addition, a utility-based analysis using a Markov model was performed to determine optimal screening ages and intervals.
Results:
The evidence synthesis identified high-certainty evidence supporting the use of the fecal immunochemical test (FIT) for reducing CRC mortality and moderate-certainty evidence for colonoscopy. Evidence for computed tomographic colonography (CTC) and stool DNA testing was rated as very low certainty. Based on the evidence review and cost-utility analysis, the committee conditionally recommends CRC screening for asymptomatic, average-risk adults aged 45–74 years using either colonoscopy every 10 years or FIT every 1–2 years. CTC and stool DNA testing were not recommended owing to insufficient evidence.
Conclusion
The 2025 Korean Guidelines for Colorectal Cancer Screening present updated, evidence-based recommendations tailored to the domestic healthcare context. By conditionally endorsing both colonoscopy and FIT for individuals aged 45–74 years, these guidelines aim to improve population-level screening effectiveness and reduce the burden of CRC in South Korea.
6.Performance of C. Diff Quik Chek Complete and RIDASCREEN immunoassays and lack of Ct value concordance between Allplex GI– Bacteria(I) and Xpert Clostridioides difficile assays: a diagnostic accuracy study
Kibum JEON ; Nuri LEE ; Hyun Soo KIM ; Han-Sung KIM ; Wonkeun SONG ; Jae-Seok KIM
Annals of Clinical Microbiology 2026;29(1):1-
Background:
Enzyme immunoassays (EIAs), which detect glutamate dehydrogenase (GDH) and toxin A/B, are widely used to screen for Clostridioides difficile infection (CDI); however, their sensitivity is lower than that of molecular assays. This study aimed to evaluate the performance of two EIAs, C. Diff Quik Chek Complete (QCC) and RIDASCREEN (RIDA), and investigate the cycle threshold (Ct) values from two real-time polymerase chain reaction (PCR) assays (Allplex GI–Bacteria(I) and Xpert C. difficile) in EIA-discordant samples.
Methods:
A total of 180 clinical stool samples were tested using QCC, RIDA, and Allplex GI– Bacteria(I) PCR assays. The Xpert C. difficile assay was used to analyze discordant results.
Results:
QCC and RIDA showed high sensitivities for GDH detection, 100.0% and 94.4%, respectively. QCC was significantly more sensitive than RIDA for toxin detection (51.4% vs. 28.6%, p = 0.007). In 25 EIA-discordant, Xpert positive samples, the Ct values of the toxin B gene ranged from 31.5 to 44.8 (mean, 38.1) for Allplex PCR and from 23.7 to 36.3 (mean, 30.4) for Xpert PCR. The Ct values of the two PCR assays were not significantly correlated (r = 0.201, p = 0.324).
Conclusion
QCC is a suitable initial immunological test for diagnosing CDI. The lack of correlation in the Ct values between the two real-time PCR assays suggests that assay-specific validation is necessary for cutoff level interpretation.
7.The Korean Rectal Cancer Multidisciplinary Committee Clinical Practice Guidelines for Rectal Cancer version 2.0
Hyo Seon RYU ; Hyun Jung KIM ; Dong Hyun KANG ; Yoo-Kang KWAK ; Han Deok KWAK ; Yoon-Hye KWON ; Dalyon KIM ; Baek-Hui KIM ; Jae Hyun KIM ; Ji Hun KIM ; Jin Won KIM ; Tae Hyung KIM ; Hae Young KIM ; Soo Min NAM ; Gyoung Tae NOH ; Jun Woo BONG ; Nak Song SUNG ; Seon Hui SHIN ; Kil-Yong LEE ; Sung Chul LEE ; Sea-Won LEE ; Jung Won LEE ; Jong Min LEE ; Myung Hoon IHN ; Joo Han LIM ; Woong Bae JI ; Dae Hee PYO ; Young Ki HONG ; Jung-Myun KWAK ;
Annals of Coloproctology 2026;42(1):4-33
Rectal cancer, which accounts for approximately 40% of colorectal cancers, remains a major clinical concern. Recent advances in diagnostic imaging, surgical techniques, radiotherapy, and systemic treatment have steadily improved rectal cancer outcomes. Considering this, the Korean Rectal Cancer Multidisciplinary (KRCM) Committee has aimed to provide clinicians and policymakers with up-to-date, evidence-based clinical practice guidelines to support optimal decision-making, reflecting current evidence, the Korean healthcare context, and patient values and preferences. The Clinical Practice Guidelines for Rectal Cancer version 2.0 were developed through multidisciplinary collaboration with related academic societies, building upon and updating the KRCM Clinical Practice Guidelines version 1.0 (titled “Multidisciplinary guidelines for the management of rectal cancer”). These consensus guidelines of the KRCM were established based on a comprehensive literature review, evidence synthesis, with recommendation development guided by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, and consideration of applicability in real-world clinical practice under the national health insurance system. Each recommendation has been presented with its strength and level of evidence.
8.Current Clinical Perspectives on Rosacea Management: Insights From a Korean Multicenter Expert Opinion Survey
Bo Ri KIM ; Sejin OH ; Ju Hee HAN ; Jimyung SEO ; Hyun-Min SEO ; Soon-Hyo KWON ; Hoon CHOI ; Jung U SHIN ; Jae We CHO ; Boncheol Leo GOO ; Jung-Im NA ; Dong Hun LEE ; Chun Pill CHOI ; HaeWoong LEE ; Joo Yeon KO ; Hwa Jung RYU ; Nark-Kyoung RHO ; Hyunjo KIM ; Ga-Young LEE ; Jong Hee LEE ; Nala SHIN ; Sang Ju LEE ; Suk Bae SEO ; Geun Soo LEE ; Hei Sung KIM ; Chang-Hun HUH
Annals of Dermatology 2026;38(1):42-50
Background:
Rosacea is a chronic inflammatory skin disorder characterized by erythema, papules, ocular symptoms, and heightened sensitivity. Patients with neurogenic symptoms such as burning or stinging remain particularly difficult to manage. Current guidelines often underrepresent energy-based devices (EBDs), pigmentary sequelae, psychosocial burden, and ocular comorbidities.
Objective:
To examine Korean dermatologists’ expert perspectives on rosacea management, focusing on skin sensitivity, neurogenic symptoms, pigmentary changes, psychosocial impact, ocular involvement, and EBD use.
Methods:
A web-based, 29-item survey was administered to 25 board-certified Korean dermatologists (May–June 2025). Quantitative and qualitative responses were analyzed.
Results:
Erythematotelangiectatic and papulopustular phenotypes with sensitivity skin predominated. EBDs (pulsed dye laser, intense pulsed light) were frequently used but limited by cost and sensitivity issues. Neurogenic symptoms were recognized but rarely treated with neuromodulators. Post-inflammatory hyperpigmentation was infrequent, yet monitoring was inconsistent.Psychosocial and ocular aspects were acknowledged but seldomly systematically addressed.Respondents expressed interest in emerging adjunctive treatments such as cold plasma, skin boosters, and holistic care approaches.
Conclusion
Korean dermatologists adopt individualized strategies for rosacea, yet practice gaps remain regarding neurogenic symptoms, pigmentary complications, and psychosocial and ocular comorbidities. Findings support the need for updated multidisciplinary, phenotype-driven guidelines aligned with real-world practice.
9.The impact of the preoperative value of phase angle in bioelectrical impedance analysis on postoperative complications after pancreaticoduodenectomy
Young Jae CHO ; Yoon Soo CHAE ; Go-Won CHOI ; Inhyuck LEE ; Younsoo SEO ; Seulah PARK ; Youngmin HAN ; Hye-sol JUNG ; Wooil KWON ; Jin-Young JANG ; Joon Seong PARK
Annals of Hepato-Biliary-Pancreatic Surgery 2026;30(1):67-75
Background:
s/Aims: Phase angle (PhA), as measured by bioelectrical impedance analysis, provides insights into hydration and nutritional status, making it a prognostic indicator of frailty. While low preoperative PhA has been linked to postoperative complications in cancer patients, its predictive value in individuals undergoing pancreaticoduodenectomy (PD) has not been thoroughly investigated.This study aims to evaluate the clinical utility of preoperative PhA in predicting postoperative complications for patients undergoing PD.
Methods:
Among 41 patients who underwent PD at Seoul National University Hospital between September and December 2024, 35 were included in the analysis after excluding 6 patients who had concomitant blood vessel or other organ resections. Patients were divided into low (Comprehensive Complication Index [CCI] ≤ 20) and high (CCI > 20) complication groups based on the CCI, derived from the Clavien–Dindo classification. The differences in PhA between the two groups were analyzed, and logistic regression was performed to assess the relationship between PhA and CCI.
Results:
The mean PhA was significantly lower in the high-CCI group compared to the low-CCI group (5.7° vs. 6.7°, p = 0.025). Multivariate logistic regression analysis indicated that PhA (odds ratio: 0.17; 95% confidence interval: 0.04–0.68; p = 0.012) was an independent predictor of high CCI. A low preoperative PhA was associated with an increased risk of postoperative complications following PD.
Conclusions
Preoperative PhA may serve as a valuable predictive indicator of postoperative complications after PD, enabling the identification of patients who could benefit from preoperative prehabilitation, including nutritional support.
10.Molecular and Phenotypic Characterization of Fluid-Derived Patient-Derived Cell and Organoid Models in Advanced Gastric Cancer
Ye Jin MOON ; Woo Sun KWON ; Chan Hee PARK ; Jinsoo JANG ; Juin PARK ; Byeong Gyu YOON ; Han Byeol MUN ; Namju KIM ; Choong-kun LEE ; Hei Cheul JEUNG ; Su-Jin SHIN ; Tae Soo KIM ; Sun Young RHA
Journal of Gastric Cancer 2026;26(2):260-278
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.

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