Third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKIs) improved outcomes in EGFR-mutant non-small cell lung cancer (NSCLC); however, the subsequent development of resistance emphasizes the necessity of overcoming this therapeutic limitation. MET amplification is one of the major resistance mechanism in EGFR-mutant NSCLC, bypassing EGFR inhibition by activating cell survival, proliferation, and metastasis. Combining MET- and EGFR-TKIs is thus emerging as a promising therapeutic strategy to overcome resistance to EGFR TKIs. This study aimed to investigate the combination of the selective MET TKI vabametkib and a third-generation EGFR TKI lazertinib in MET-amplified EGFR TKI resistance models. Inhibition of downstream signaling and cell proliferation by vabametkib plus lazertinib were evaluated in osimertinib-resistance NSCLC cell lines (HCC827-AR) and patient-derived organoid (YUO-010) by western blot and Cell Titer-Glo assay. In vitro studies demonstrated that vabametkib plus lazertinib synergistically inhibited EGFR/MET phosphorylation, leading to markedly enhanced anti-proliferative effects through downstream PI3K/AKT and MAPK pathway blockade. To investigate the antitumor effects in in vivo, we employed two patient-derived xenograft (PDX) models (YHIM-1035(1) and YHIM-1053) harboring MET amplification, as characterized by whole-exome sequencing or droplet digital PCR (ddPCR). Consistent with the in vitro findings, treatment with vabametkib plus lazertinib produced pronounced suppression of tumor growth in both models through a synergistic mechanism. These findings establish vabametkib plus lazertinib as a promising strategy for MET-amplified NSCLC, currently under evaluation in an ongoing phase II clinical trial (NCT05541822).

L-MIND trial has demonstrated efficacy of tafasitamab plus lenalidomide in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). However, real-world evidence comparing tafasitamab plus lenalidomide to standard salvage therapies remains limited. Therefore, we conducted an external control arm study to evaluate clinical effectiveness of tafasitamab plus lenalidomide compared with ICE (ifosfamide, carboplatin, etoposide) regimen in South Korea. Individual patient-level data from L-MIND trial and Samsung Medical Center-Lymphoma Cohort Studies (SMC-LCS) registry in South Korea were analyzed to identify DLBCL patients who received tafasitamab plus lenalidomide or ICE as second- to fourth-line therapy. Primary endpoint was overall survival (OS), while secondary endpoints included progression-free survival (PFS), time to next treatment (TTNT), duration of response (DoR), objective response rate (ORR), and complete response rate (CRR). After applying inverse probability of treatment weighting (IPTW), time-to-event and binary outcomes were analyzed using Cox and logistic regression models, respectively. A total of 76 patients in L-MIND and 39 patients in SMC-LCS were analyzed. After IPTW, median OS was 34.1 months (95% CI, 18.6-NR) for tafasitamab plus lenalidomide and 6.4 months (0.3-13.9) for ICE (hazard ratio [HR], 0.33; 95% CI, 0.20-0.53). HRs were 0.33 (95% CI, 0.20-0.54) for PFS, 0.42 (0.26-0.66) for TTNT, and 0.17 (0.08-0.35) for DoR. Odds ratios were 3.17 (1.37-7.32) for ORR, and 2.87 (1.06-7.78) for CRR. Tafasitamab plus lenalidomide showed favorable outcomes over ICE, suggesting a clinically meaningful treatment option for r/r DLBCL in South Korea.

Glioblastoma (GBM) is an aggressive primary brain tumor marked by a poor prognosis and limited effectiveness of current therapies, which are often accompanied by substantial recurrence rates. To address this challenge, we developed BM03, an engineered mesenchymal stem cell (MSC) line specifically designed for glioblastoma therapy. BM03 is structured to enhance migration to GBM sites and deliver targeted, multimodal gene-based therapies. This cell line was developed by transducing bone marrow-derived MSCs with lentiviral vectors to enable (1) continuous growth through immortalization, (2) tumor-targeted migration via GBM-associated chemokine receptors CCR2 and CXCR4, and (3) direct tumoricidal effects through TRAIL and CD::UPRT gene expression for apoptosis and prodrug activation. BM03 demonstrated strong chemotaxis toward GBM cells in both in vitro and in vivo models, facilitated by CCR2 and CXCR4 co-expression, which was maintained through tetracycline transactivator (tTA)-mediated transcriptional control. The combination of TRAIL and CD::UPRT showed significant cytotoxicity, effectively overcoming TRAIL resistance in GBM cells and exhibiting enhanced antitumor effects in a GBM mouse xenograft model. Moreover, repeated BM03 administration, particularly when combined with temozolomide (TMZ), resulted in sustained tumor regression and improved survival. To enhance clinical relevance, we evaluated intraventricular administration, which effectively bypasses the blood-brain barrier and targets dispersed GBM lesions. This study establishes BM03 as a potent, safe, and multifunctional stem cell platform with potential to advance targeted GBM therapy through improved migration, multimodal cytotoxicity, and a strategic administration route for enhanced therapeutic efficacy.

This study aimed to project cancer incidence and mortality for 2026 to estimate Korea's current cancer burden. Cancer incidence data from 1999 to 2023 were obtained from the Korea National Cancer Incidence Database, while cancer mortality data from 1993 to 2024 were acquired from Ministry of Data and Statistics. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and then by the projected age-specific rates by the anticipated age-specific population for 2026. A joinpoint regression model was applied to identify significant changes in trends, using only the most recent trend data for predictions. A total of 308,876 new cancer cases and 86,317 cancer deaths are expected in Korea in 2026. The most commonly diagnosed cancer is projected to be thyroid cancer, followed by the colorectal, lung, breast, prostate and stomach cancers. These six cancers are expected to account for 63.5% of all newly diagnosed cancers. Lung cancer is expected to be the leading cause of cancer-related deaths, followed by liver, colorectal, pancreatic, gallbladder, and stomach cancers, together comprising 65.9% of all cancer deaths. Korea's cancer burden continues to shift toward malignancies prevalent in older populations. The sustained increase in prostate cancer among men and the rising mortality impact of pancreatic cancer reflect structural changes in the national cancer profile amid rapid population aging.

The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2023, with international comparisons. Cancer incidence, survival, and prevalence rates were calculated using the Korea National Cancer Incidence Database (1999-2023), with survival follow-up until December 31, 2024. Mortality data were obtained from the Ministry of Data and Statistics, while international comparisons were based on GLOBOCAN data. In 2023, 288,613 newly diagnosed cancer cases (age-standardized rate [ASR], 288.6 per 100,000) and 85,271 deaths from cancer (ASR, 64.3 per 100,000) were reported. Among the incident cases, 145,452 (50.4%) were aged 65 years or older. Prostate cancer became the most common cancer among men for the first time. The proportion of localized-stage cancers increased from 45.6% in 2005 to 51.8% in 2023. Korea had the lowest cancer mortality among countries with similar incidence rates and the lowest mortality-to-incidence ratios for stomach, colorectal, and breast cancer. The 5-year relative survival rate (2019-2023) was 73.7% overall and 92.7% for localized-stage cancers. Over 2.73 million prevalent cases were identified in 2023, representing 5.3% of the Korean population. These findings indicate that Korea's cancer control efforts have contributed to early detection and improved survival outcomes. As Korea enters a super-aged society in 2025, cancer burden will continue to increase, requiring sustained and adaptive cancer control strategies.

Brain metastases are a serious complication in non-small cell lung cancer (NSCLC). However, data regarding efficacy of immune checkpoint inhibitors and chemotherapy combinations are limited. This phase II study aimed to evaluate the intracranial efficacy and safety of pembrolizumab and chemotherapy in treatment-naïve NSCLC patients with asymptomatic brain metastases. This single-arm, phase II trial was conducted at Samsung Medical Center, Korea. Eligible patients had stage IV NSCLC with asymptomatic, untreated brain metastases and no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alterations. Patients received pembrolizumab with chemotherapy every 3 weeks for 4 cycles, followed by pembrolizumab with or without maintenance chemotherapy up to 35 cycles. The primary endpoint was intracranial objective response rate (icORR). Secondary endpoints included intracranial progression free survival (icPFS), intracranial duration of response (icDoR), objective response rate (ORR), progression free survival (PFS), overall survival, and safety. Between February 2021 and June 2024, a total of 13 patients were enrolled. Due to challenges in recruiting patients, enrollment was discontinued after the 13 patients. The icORR was 46.2% (95% CI, 19.2-74.8), with 6 patients achieving partial response. The median icPFS was 9.8 months (95% CI, 5.2-21.5), and median icDoR was 9.3 months (95% CI, 4.0-20.3). Median PFS and overall survival was 7.2 months (95% CI, 2.4-12.3) and 10.7 months (95% CI, 7.2-21.5), respectively. Most treatment-related adverse events were grade 1-2." Pembrolizumab combined with chemotherapy demonstrated encouraging intracranial activity and manageable safety profile in NSCLC patients with untreated, asymptomatic brain metastases.

This study aimed to compare the clinical outcomes and costs of robotic-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) in patients undergoing minimally invasive anatomical resection for primary lung cancer. A retrospective analysis was conducted on 2,086 patients who underwent surgery at a single institution from January 2017 to July 2020, including 134 RATS and 1,952 VATS cases. Propensity score matching (PSM) was applied, resulting in 268 matched patients (134 RATS and 134 VATS). Cost data were obtained from hospital billing files, encompassing 20 categories, including total hospitalization fees, anesthesia fees, surgery fees, costs of surgical instruments and materials, and general examination fees. After PSM, RATS patients had a shorter median postoperative stay (5 days vs. 6 days, p = 0.009) and lower thoracotomy conversion rate (1.5% vs. 14.9%, p < 0.001) than VATS. However, RATS incurred higher total costs by an average of $1,230 (p < 0.001), mainly due to increased surgical expenses ($1,163, p < 0.001). In multivariate analysis, RATS (12.41%, p < 0.001), neoadjuvant therapy (13.3%, p = 0.005), complications (4.2%, p < 0.001), and length of stay (2.0%, p < 0.001) were found to be associated with higher costs. Although RATS has been shown to reduce the thoracotomy conversion rate and length of hospital stay, it incurs higher costs than VATS, primarily due to increased surgical expenses. The justification for RATS should be further evaluated through sustainability and cost-effectiveness studies with long-term follow-up.

Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. CD103+ tissue-resident memory T (TRM) cells are crucial for anti-tumor immunity in TNBC. We investigated whether their spatial interactions with other T-cells influence clinical outcomes, particularly following neoadjuvant chemotherapy (NAC). This retrospective study analyzed 182 TNBC patients (98 NAC-treated; 84 non-NAC). Using Opal™ multiplex immunohistochemistry data and the Spatial Image Analysis of Tissues (SPIAT) R package, we analysed spatial interactions between CD103+ cells and other T cell subsets (CD45RO, CD8, CD4, PD-1) in central/peripheral tumor regions. Normalized mixing score (NMS) quantified spatial interactions. NMS-based clustering revealed two distinct CD103+ cell interaction patterns-Cluster 1 (low NMS) characterized by weaker and Cluster 2 (high NMS) by stronger spatial interactions between CD103+ and other T cell subsets. In the NAC group, Cluster 2 in the tumor periphery was associated with lower pathologic stage (p=0.002), higher stromal tumor-infiltrating lymphocyte level (p=0.031), and significantly improved recurrence-free survival (p=0.028) and overall survival (p=0.018) compared to Cluster 1. Central tumor region clustering patterns had no association with prognosis. No significant survival-related differences were observed in the non-NAC group according to NMS-based clustering. Spatial interaction patterns between CD103+ and other T cell subsets in the tumor periphery influence clinical outcomes in NAC-treated TNBC patients. Analysing such spatial relationships between T cells, rather than their presence alone, may provide additional prognostic information for patients undergoing NAC.

To develop the 2025 update to the Korean colorectal cancer (CRC) screening guidelines by systematically assessing recent evidence, integrating domestic data, and addressing changes since the 2015 guideline revision, and accordingly, provide an evidence-based standard for clinicians and policymakers. A multidisciplinary committee developed the guidelines using the Grading of Recommendations, Assessment, Development and Evaluation methodology. The process involved establishing three Key Questions (KQs) focused on efficacy, accuracy, and optimal age and interval for screening. A systematic review of international guidelines and primary literature (327 studies included) was conducted. A utility-based analysis using the Markov model was also performed to determine optimal screening ages and intervals. The review identified high-certainty evidence for Fecal Immunochemical Test (FIT) in reducing CRC mortality and moderate-certainty evidence for colonoscopy. Evidence for CT colonography (CTC) and stool DNA testing showed very low certainty. Based on this synthesis and cost-utility analysis, the committee conditionally recommends 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. The 2025 Korean Guidelines for Colorectal Cancer Screening provide the latest evidence-based recommendations tailored to the domestic context. By conditionally adopting both colonoscopy and FIT for individuals aged 45-74 years, these guidelines aim to optimize public health outcomes and reduce the colorectal cancer burden in South Korea.

To investigate the 5-year conditional relative survival and competing mortality in surgically treated patients with localized and regional kidney cancer. Using a nationwide population-based database, the Korea Clinical Data Utilization Network for Research Excellence, conditional relative survival conditioned on 1 to 3 years of survival after diagnosis was measured. These rates were stratified by age, sex, socioeconomic status, comorbidities, and treatment received. Cause of death and estimated cause-specific mortality were also described and considered with competing risks. This study included a total of 19,749 newly diagnosed patients with kidney cancer who underwent surgical treatment from 2013 to 2019. The baseline conditional relative survival rates for the entire cohort, patients with localized disease, and patients with regional disease were 97.2%, 99.4%, and 82.6%, respectively. After one year, these rates increased to 99.4%, 100.0%, and 95.3%, respectively. Patients who underwent surgery only had the highest baseline conditional relative survival rates (99.3%) compared with those who received surgery with radiotherapy (74.0%), with chemotherapy (38.9%), and with chemotherapy and radiotherapy (16.2%). Specifically, patients who underwent robotic surgery or partial nephrectomy showed higher baseline conditional relative survival rates (>100%) than others. Furthermore, kidney cancer was the leading cause of death (49.6%), followed by other types of cancer and cardiovascular disease. Over time, kidney cancer-specific mortality decreased. Conditional survival after surgery for localized or regional kidney cancer was high and improved over time. These findings indicate that long-term prognosis varies by stage and patient characteristics and should inform postoperative surveillance.