Cancer Res Treat [JOURNAL]
Sun
200 papers
RMRP-Induced Chemo-Resistance in Relapsed and Refractory Acute Myeloid Leukemia via Mitochondrial Dysfunction.
Zhao Y, Guo H, Zhou Y … +2 more , Niu LT, Wu N
Cancer Res Treat · 2025 Aug · PMID 40776559 · Publisher ↗
PURPOSE: Relapsed and refractory acute myeloid leukemia (R/R AML) has a poor prognosis due to chemotherapy resistance. Mitochondrial dysfunction contributes to this resistance, but the role of the RNA component of mitoch...
PURPOSE: Relapsed and refractory acute myeloid leukemia (R/R AML) has a poor prognosis due to chemotherapy resistance. Mitochondrial dysfunction contributes to this resistance, but the role of the RNA component of mitochondrial RNA processing endoribonuclease (RMRP) in R/R AML remains unclear. MATERIALS AND METHODS: Mass spectrometry identified molecules linked to chemoresistance in AML. The role of RMRP was examined by assessing its impact on mitochondrial transfer in the AML bone marrow microenvironment. Transmission electron microscopy and western blotting were used to study mitochondrial function and autophagy in RMRP-knockdown AML cells. RESULTS: RMRP was overexpressed in R/R AML, and its silencing sensitized AML cells to chemotherapy drugs. RMRP knockdown reduced mitochondrial respiratory capacity, mtDNA copy numbers, and mitochondrial gene transcription. It also led to altered mitophagy markers and decreased mitochondrial methylation. Immunoprecipitation revealed RMRP-TERT complex formation, suggesting a role in post-transcriptional regulation of mitochondrial function and ROS production. CONCLUSION: High RMRP expression in R/R AML is linked to mitochondrial dysfunction and chemotherapy resistance, providing new insights into potential therapeutic strategies to overcome drug resistance in this disease.
A Novel CD58 Mutation-Related Signature Predicts Prognosis Risk in Diffuse Large B-Cell Lymphoma Patients.
Wang HL, Shang CY, Hua W … +12 more , Yin H, Li Y, Liang JH, Gao R, Pan BH, Zhang XY, Wu JZ, Shen HR, Wang L, Li JY, Liang JH, Xu W
Cancer Res Treat · 2025 Jul · PMID 40744814 · Publisher ↗
PURPOSE: CD58, a ligand of the CD2 receptor on T cells and NK cells, is abnormally expressed in diffuse large B-cell lymphoma (DLBCL). However, data on the value of CD58 mutation (CD58mut) in DLBCL are limited. Here, we...
PURPOSE: CD58, a ligand of the CD2 receptor on T cells and NK cells, is abnormally expressed in diffuse large B-cell lymphoma (DLBCL). However, data on the value of CD58 mutation (CD58mut) in DLBCL are limited. Here, we aimed to evaluate the characteristics and prognostic value of CD58mut in DLBCL patients. MATERIALS AND METHODS: The available clinical information and corresponding mutation data of DLBCL were obtained from published articles. Ultimately, 3025 DLBCL patients in published cohorts were enrolled in the final analysis. Among the 202 DLBCL patients in the Jiangsu Province Hospital (JSPH) cohort, all tumor tissue samples were collected to perform NGS and gene expression were analyzed via RNA-seq. RESULTS: We found that 8.2% (250/3025) of patients were CD58mut in integrated cohort, whereas 11.3% (23/202) in JSPH cohort. CD58mut patients exhibit inferior progression-free survival (PFS) (the integrated cohort: HR=0.96,95% CI:0.77-1.20, p=0.663 the JSPH cohort: HR=1.85,95% CI:0.85-4.04, p=0.052) and overall survival (OS) (the integrated cohort: HR=1.43,95% CI:1.15-1.77, p<0.001; the JSPH cohort: HR=2.40,95% CI:0.83-6.93, p=0.026). A model based on six signature genes (MRO, OXTR, RASL11A, RLN1, SIGLEC1 and PROM2) was constructed via machine learning. To optimize risk stratification and survival prediction for CD58mut patients, biological mechanism of the poorer prognosis in high-risk group may be related to the greater abundance of immunosuppressive cells, especially M2 macrophages. CONCLUSION: Our results indicated that CD58mut could serve as a novel prognostic factor for DLBCL patients, and further exploration of personalized treatment strategies for high-risk DLBCL patients based on the risk score model is needed.
Proteomic Analysis Identifies Association of Periostin, a Matricellular Protein, with High Tumor Stroma and Immune Exclusion in Triple-Negative Breast Cancer.
Jeon Y, Lee G, Jeong BK … +5 more , Kim YY, Kim J, Jeong JH, Kim K, Lee HJ
Cancer Res Treat · 2025 Jul · PMID 40744813 · Publisher ↗
PURPOSE: Immune excluded/desert tumors show reduced responsiveness to immunotherapy compared to inflamed tumors. The tumor stroma contributes to immune evasion. This study aimed to identify proteins overexpressed in tumo...
PURPOSE: Immune excluded/desert tumors show reduced responsiveness to immunotherapy compared to inflamed tumors. The tumor stroma contributes to immune evasion. This study aimed to identify proteins overexpressed in tumors with high tumor stroma among immune excluded triple-negative breast cancer (TNBC) to better understand the mechanisms of immune exclusion. MATERIALS AND METHODS: Proteomic analysis was conducted on formalin-fixed, paraffin-embedded samples from 403 cases of TNBC. We compared protein expression between stroma high vs. stroma low within the immune excluded subtype. We investigated the correlations between the identified protein expression and other clinicopathologic features. Immunohistochemical (IHC) staining and single-cell analysis were conducted, along with survival analysis. RESULTS: Among the 247 eligible cases, 81 (32.8%) were classified as immune excluded and 166 (67.2%) as inflamed. Within the excluded subtype, periostin was the only extracellular matrix-related protein significantly overexpressed in stroma high cases. Periostin expression demonstrated a positive correlation with the amount of stroma (r = 0.51, p<0.001) and a negative correlation with tumor-infiltrating lymphocytes (TILs) (r = -0.30, p<0.001). Periostin expression in the tumor stroma was confirmed by IHC. Single-cell analysis demonstrated that periostin originated from cancer-associated fibroblasts (CAFs). High periostin levels correlated with poorer recurrence-free survival (hazard ratio 1.422, p=0.005). CONCLUSION: Periostin is overexpressed in stroma high, immune excluded TNBC and is derived from CAFs. Its expression is associated with reduced TILs and poor prognosis. The development of targeted agents against periostin-positive CAFs may help overcome immune evasion and improve the effectiveness of immunotherapy in TNBC.
Combination of Niraparib and Lapatinib for Ovarian Cancer Treatment.
Jiang F, Liu X, Wei Y … +4 more , Ding Y, Cai W, Xu S, Tang B
Cancer Res Treat · 2025 Jul · PMID 40744812 · Publisher ↗
PURPOSE: Ovarian cancer is characterized by high malignancy, frequent recurrence with drug resistance, and poor five-year survival rates. Although PARP inhibitors like niraparib show efficacy in homologous recombination...
PURPOSE: Ovarian cancer is characterized by high malignancy, frequent recurrence with drug resistance, and poor five-year survival rates. Although PARP inhibitors like niraparib show efficacy in homologous recombination repair-deficient (HRD) ovarian cancer, resistance often develops. This study aimed to evaluate the synergistic therapeutic potential of combining the EGFR inhibitor lapatinib and the PARP inhibitor niraparib to evaluate combinatorial effects and enhance antitumor effects in ovarian cancer. MATERIALS AND METHODS: Lapatinib (EGFR inhibitor) and niraparib (PARP inhibitor) were screened from the FDA/CFDA-approved drug library. In vitro assays assessed ovarian cancer cell proliferation, clonogenicity, metastatic ability, and apoptosis. Mechanistic studies analyzed phosphorylation levels of EGFR, AKT, and ERK via biochemical assays. In vivo experiments were conducted to validate the antitumor efficacy of the drug combination. RESULTS: The lapatinib-niraparib combination synergistically suppressed ovarian cancer cell proliferation, inhibited clonogenic formation and metastasis, and induced apoptosis. Mechanistically, the dual therapy reduced phosphorylation of EGFR, AKT, and ERK, indicating suppression of downstream signaling pathways. Both in vitro and in vivo experiments demonstrated significant inhibition of ovarian cancer growth with the combination treatment. CONCLUSION: EGFR/HER2-expressing ovarian cancer cells responded to lapatinib and that a synergistic effect was observed when combined with niraparib. These findings highlight its promising clinical potential for improving outcomes in ovarian cancer patients.
Pancreatic Irradiation Dose as a Risk Factor for Elevation in Hemoglobin A1c Level and Diabetes Mellitus in Patients with Indolent Gastroduodenal Lymphoma.
Baek JY, Lim DH, Oh D … +4 more , Kim JJ, Lee JH, Min BH, Lee H
Cancer Res Treat · 2025 Jul · PMID 40744811 · Publisher ↗
PURPOSE: This study investigated the association between pancreatic irradiation dose and HbA1c elevation in patients with indolent gastroduodenal lymphomas treated with radiotherapy (RT). MATERIAL AND METHODS: We retrosp...
PURPOSE: This study investigated the association between pancreatic irradiation dose and HbA1c elevation in patients with indolent gastroduodenal lymphomas treated with radiotherapy (RT). MATERIAL AND METHODS: We retrospectively reviewed 103 patients treated at Samsung Medical Center between 2010 and 2023, with or without RT. Patients were stratified by mean pancreas dose (<2300 cGy vs. ≥2300 cGy). The primary outcome was the 2-year HbA1c elevation, with additional time-to-event analyses for HbA1c elevation ≥0.5% and diabetes mellitus (DM) development. RESULTS: RT was administered to 62 (60.2%) patients, while 41 (39.8%) did not receive RT. There was no significant difference in baseline characteristics except for cancer type. Patients with a mean pancreas dose ≥2300 cGy had a significantly greater 2-year HbA1c increase than those receiving <2300 cGy (p=0.003) or no RT (p<0.001). No significant difference was found between patients receiving <2300 cGy and those without RT (p=0.120). In multivariate time-to-event analysis, a mean pancreas dose ≥2300 cGy was the sole significant risk factor for an HbA1c increase ≥0.5% (p<0.001), while mean pancreas dose <2300 cGy did not show a significant effect (p=0.851). Furthermore, a mean pancreas dose ≥2300 cGy (p=0.017) and baseline prediabetes (HbA1c ≥5.7%) (p=0.023) were independent predictors of DM development. CONCLUSION: A mean pancreas dose ≥2300 cGy was associated with HbA1c elevation, whereas doses <2300 had minimal effect. Given the established link between higher HbA1c level and increased risk of DM and cardiovascular events, pancreatic dose reduction should be considered in RT planning for patients with an expected good prognosis.
Real-World Efficacy and Safety of Teclistamab for Patients with Relapsed or Refractory Multiple Myeloma: Nationwide Retrospective Analysis of the Named Patient Program in Korea.
Yi JH, Lee JH, Jung SH … +9 more , Lee JH, Lee JY, Kim K, Park SS, Min CK, Choi YS, Kim MK, Yhim HY, Yoon DH
Cancer Res Treat · 2025 Jul · PMID 40744810 · Publisher ↗
PURPOSE: The prognosis for heavily pretreated patients with relapsed or refractory multiple myeloma (RRMM) remains poor. Teclistamab, a bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3, has demonstr...
PURPOSE: The prognosis for heavily pretreated patients with relapsed or refractory multiple myeloma (RRMM) remains poor. Teclistamab, a bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3, has demonstrated deep and durable responses in triple-class exposed RRMM patients in the MajesTEC-1 trial. To further evaluate the efficacy and safety of teclistamab in Korean patients, we conducted a nationwide retrospective analysis. MATERIALS AND METHODS: In August 2022, a Named Patient Program (NPP) for teclistamab was initiated in Korea. The inclusion and exclusion criteria, dosage, treatment schedule, and dose modification protocols were largely consistent with those of the MajesTEC-1 trial. Retrospective data were collected for 42 patients who participated in the program. RESULTS: The median age was 67 years (range, 48-84), and the median number of prior lines of therapy was 6 (range, 3-10). Triple- and penta-class refractoriness were observed in 40.5% and 19.0% of patients, respectively. The overall response rate was 66.7% (28/42); 17 patients (40.5%) achieved a complete or deeper response. With a median follow-up of 16.4 months, the median progression-free survival (PFS) was 14.1 months. Patients with R-ISS stage III exhibited significantly shorter PFS (3.1 months vs. not reached, p=0.041). The 12-month overall survival rate was 61.7%; disease progression and infection were the most common causes of death. Only one patient experienced grade ≥ 3 cytokine release syndrome (CRS), and no cases of immune effector cell-associated neurotoxicity syndrome were reported. Grade ≥ 3 infections occurred in 42.9% (n=18) of patients and frequently led to treatment interruption (n=18). CONCLUSION: Efficacy outcomes including rapid responses, a high response rate, and prolonged survival duration as well as safety profiles, including the incidence of infections, CRS were comparable to those observed in the MajesTEC-1 trial. Given the historically poor outcomes observed in patients with triple-class exposed RRMM, teclistamab treatment should be strongly considered for these patients.
BTG1 Mutation Correlates with Inferior Prognosis in Diffuse Large B-Cell Lymphoma.
Shang CY, Hua W, Xing TY … +10 more , Du KX, Wu YF, Li Y, Yin H, Shen HR, Wang L, Li JY, Gao R, Xu W, Liang JH
Cancer Res Treat · 2025 Jul · PMID 40744809 · Publisher ↗
PURPOSE: B celltranslocation gene 1 (BTG1) is a highly conserved gene and recurrently mutated in the MCD subtype of diffuse large B-cell lymphoma (DLBCL). The specific enrichment of BTG1 mutation (BTG1mut) raises a potent...
PURPOSE: B celltranslocation gene 1 (BTG1) is a highly conserved gene and recurrently mutated in the MCD subtype of diffuse large B-cell lymphoma (DLBCL). The specific enrichment of BTG1 mutation (BTG1mut) raises a potential hypothesis that they may actively contribute to DLBCL. However, the biological characteristics and prognostic significance of BTG1 in DLBCL remain to be explored. Therefore, the objective of our study was to evaluate the value of BTG1 in DLBCL. MATERIALS AND METHODS: The available clinical information and corresponding mutation data of DLBCL were obtained from published articles. Tumor tissue samples of DLBCL patients diagnosed in Jiangsu Province Hospital (JSPH) from 2021 to 2023 were collected for NGS, 195 samples were analyzed the gene expression levels using RNA-seq, among them, 40 samples were analyzed by untargeted metabolomic. RESULTS: We enrolled 2,379 DLBCL patients from 5 published studies and 243 DLBCL patients from Jiangsu Province Hospital (JSPH) cohort. 11.0% (262/2379) of patients were BTG1mut in external cohort, compared with 25.1% (61/243) in the JSPH cohort. BTG1mut was associated with adverse clinical features and was prone to involve testis. Patients with BTG1mut exhibit inferior overall survival (OS). Furthermore, pathway enrichment analysis of the untargeted metabolomic showed that several meaningful pathways have been found such as amino acid metabolism and lipid metabolism. CONCLUSION: BTG1 mutation was promising prognostic predictor for DLBCL. The mechanism driving different survival outcomes may be attributed to the tumor metabolic reprogramming.
Microbial Dynamics Across Molecular Subtypes and Prognostic Significance of Lactobacillus in Gastric Cancer.
Nam SK, Park J, Oh S … +9 more , Kwak Y, Shin CM, Park KU, Kwon NJ, Kong SH, Park DJ, Lee HJ, Yang HK, Lee HS
Cancer Res Treat · 2025 Jul · PMID 40707023 · Publisher ↗
PURPOSE: Recent studies have revealed a diverse gastric microbiota beyond Helicobacter pylori, suggesting a role in gastric cancer (GC). We aimed to investigate the composition and characteristics of the microbiota in GC...
PURPOSE: Recent studies have revealed a diverse gastric microbiota beyond Helicobacter pylori, suggesting a role in gastric cancer (GC). We aimed to investigate the composition and characteristics of the microbiota in GC and non-cancerous gastric mucosa (NC), with a particular focus on their relationship to molecular subtypes. MATERIALS AND METHODS: We conducted 16S rRNA sequencing and whole transcriptomic analysis on fresh-frozen GC and NC tissue samples from 192 GC patients, as well as saliva samples from 12 GC patients and 18 healthy individuals. Microsatellite instability (MSI), Epstein-Barr virus (EBV) in situ hybridization, and immunohistochemistry for p53 and E-cadherin were used to define molecular subtypes. RESULTS: GC tissues exhibited significantly higher diversity compared to matched NC tissues, with microbial profiles marked by decreased Helicobacter and increased Streptococcus, Prevotella, and Lactobacillus. Saliva samples predominantly contained oral bacteria and exhibited distinct microbial profiles from gastric tissues. In GC tissue, Helicobacter abundance was negatively correlated with key immune checkpoint genes (CTLA-4, PDCD1, CD274, and LAG3), whereas Prevotella, Streptococcus, and Fusobacterium were positively correlated. MSI-high and EBV-positive subtypes showed lower levels of Helicobacter but higher levels of Lactobacillus, Prevotella, and Streptococcus compared to the epithelial-mesenchymal transition (EMT)-like subtype. Notably, within MSI-H GC, a subgroup characterized by Lactobacillus-enriched and otherwise microbiota-depleted profiles was significantly associated with poorer overall and disease-free survival. CONCLUSION: These findings underscore distinct microbial patterns across GC molecular subtypes, suggesting potential biomarkers for GC diagnosis and treatment.
Characteristics of Immune Checkpoint Inhibitor (ICI)-Related Hepatotoxicity Based on the Baseline Liver Function.
Jung WJ, Jo EJ, Kim YJ … +9 more , Park M, Kim E, Jung YS, Park SR, Oh JS, Kim SH, Park J, Jung SY, Jeon N
Cancer Res Treat · 2025 Jul · PMID 40707022 · Publisher ↗
PURPOSE: This study estimated the incidence of immune checkpoint inhibitor-related hepatotoxicity (ICH), identified risk factors, and characterized patients who developed ICH. MATERIALS AND METHODS: Adult patients treate...
PURPOSE: This study estimated the incidence of immune checkpoint inhibitor-related hepatotoxicity (ICH), identified risk factors, and characterized patients who developed ICH. MATERIALS AND METHODS: Adult patients treated with ICIs from January 2015 to June 2022 in a tertiary hospital were included, excluding those without liver function tests or those with liver cancer but normal baseline liver function. Patients were stratified by baseline liver function status; in overall and each of stratified cohorts ICH incidence was calculated as the number of events per 100 person-years with grade 3 hepatotoxicity as the primary outcome. Patient characteristics were assessed using descriptive statistics, and risk factors were identified through multivariable Cox regression. Causality between ICI use and hepatotoxicity was assessed using the Naranjo Algorithm. RESULTS: Among 803 patients, the ICH incidence was 19.5 cases per 100 person-years, with a higher incidence (47.3 vs. 9.3 cases per 100 person-years) and earlier onset (13 vs. 15 days) in the abnormal compared to the normal group. Significant risk factors for ICH included female sex in the normal group and liver cancer in the abnormal group. According to the Naranjo Algorithm, all the 60 ICH cases were classified as "probable" or "possible". Among the 60 cases, 62% (n=37) resulted in ICI discontinuation. The baseline liver function did not impact on the severity or the likelihood of ICI discontinuation. CONCLUSION: Future studies are needed to evaluate whether the impact of ICI discontinuation on survival outcomes in patients with ICH varies based on baseline liver function abnormalities.
Comparative Effectiveness of Anbalcabtagene Autoleucel versus Tisagenlecleucel in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma.
Seo HJ, Yoo WH, Jung K … +4 more , Kim JW, Shin JY, Kim JH, Kim WS
Cancer Res Treat · 2025 Jul · PMID 40665713 · Publisher ↗
PURPOSE: Anbalcabtagene autoleucel (anbal-cel) is a second-generation CD19-targeted chimeric antigen receptor-T cell therapy reducing T-cell exhaustion through PD-1 and TIGIT downregulation. We compared efficacy of anbal...
PURPOSE: Anbalcabtagene autoleucel (anbal-cel) is a second-generation CD19-targeted chimeric antigen receptor-T cell therapy reducing T-cell exhaustion through PD-1 and TIGIT downregulation. We compared efficacy of anbal-cel with tisagenlecleucel (tisa-cel) in relapsed/refractory diffuse large B-cell lymphoma using external control arm study design. MATERIALS AND METHODS: We performed a matching-adjusted indirect comparison (MAIC) using individual patient data from CRC01-01 (NCT#04836507) and aggregate data from JULIET trial (NCT#02445248). Primary outcomes were overall survival (OS) and progression free-survival (PFS), with corresponding hazard ratio (HR) and 95% confidence interval (CI) assessed using weighted Cox proportional hazard model. Secondary outcomes were objective response rate (ORR) and complete response rate (CRR), with corresponding odds ratio (OR) and 95% CI assessed using weighted logistic regression model. RESULTS: We included 79 patients in CRC01-01 and 115 in JULIET trial. In naïve comparison, median OS was not reached (NR; 95% CI 13.1-NE) for anbal-cel versus 11.1 months (6.6-23.9) for tisa-cel, corresponding to HR of 0.54 (0.34-0.87). Median PFS was 5.5 months (4.2-16.2) versus 2.9 months (2.3-5.2) with HR of 0.73 (0.50-1.08). ORR was 73.4% versus 53.0% with OR of 2.45 (1.32-4.54), and CRR was 64.6% versus 39.1% with OR of 2.83 (1.56-5.13). After applying MAIC to balance prognostic factors between the groups, adjusted HRs or ORs were 0.47 (0.23-0.95) for OS, 0.59 (0.36-0.96) for PFS, 2.60 (1.04-6.52) for ORR, and 3.00 (1.30-6.92) for CRR. CONCLUSION: Anbal-cel showed superior effectiveness over tisa-cel, with higher response rates and improved survival outcomes, even after accounting for imbalances in prognostic factors at trial enrollment.
Keratin 6A Overexpression in the Lymphovascular Invasion-Associated Tumor Subgroup Promotes Progression of Triple-Negative Breast Cancer.
Luo W, Zou Y, Jiang Y … +11 more , Ma X, Guo S, Wang Y, Liu Y, Hai L, Jia W, Liu W, Meng R, Cao X, Ruan X, Yu Y
Cancer Res Treat · 2025 Jul · PMID 40665712 · Publisher ↗
PURPOSE: Lymphovascular invasion (LVI) is a strong predictor of poor prognosis in triple-negative breast cancer (TNBC), yet its molecular basis remains unclear. This study investigates epithelial regulators associated wi...
PURPOSE: Lymphovascular invasion (LVI) is a strong predictor of poor prognosis in triple-negative breast cancer (TNBC), yet its molecular basis remains unclear. This study investigates epithelial regulators associated with LVI and their functional roles in TNBC progression. MATERIALS AND METHODS: We utilized single-cell sequencing data to further characterize epithelial cell populations in TNBC, identifying dominant epithelial clusters in LVI-positive TNBC tissues. The prognostic significance of dominant epithelial marker genes was explored through transcriptomic analysis and immunohistochemical staining of patient samples from our center. Additionally, the effects of the marker gene on TNBC cell invasion and metastasis were validated in vitro and in vivo. RESULTS: Single-cell data analysis revealed nine distinct epithelial cell clusters within TNBC tissues. Among these, Cluster 4 was identified as the dominant epithelial subpopulation in LVI-positive TNBC, marked by the prognostic gene KRT6A. Multiple datasets confirmed KRT6A as a crucial prognostic marker in TNBC. Functional assays, including CCK8, wound healing, transwell assays, and animal experiments, demonstrated that KRT6A knockdown significantly impaired the proliferation, invasion, and metastatic potential of TNBC cells. Mechanistically, KRT6A promoted epithelial-mesenchymal transition (EMT) and activated Wnt/β-catenin signaling by stabilizing β-catenin through GSK3β phosphorylation. CONCLUSION: KRT6A promotes EMT and metastasis in TNBC via Wnt/β-catenin signaling, contributing to LVI and chemoresistance. It may serve as a prognostic biomarker and therapeutic target in TNBC.
Barriers to Clinical Trial Enrollment: KCSG Survey-Based Perspectives of Medical Oncologists, Patients, and Their Caregivers.
Maeng CH, Park I, Lee IH … +3 more , An HJ, Shim HJ, Lee SC
Cancer Res Treat · 2025 Jul · PMID 40635454 · Publisher ↗
PURPOSE: Despite the critical role of clinical trials in advancing cancer treatment, patient enrollment remains challenging in South Korea. We aimed to identify key barriers to clinical trial participation from the persp...
PURPOSE: Despite the critical role of clinical trials in advancing cancer treatment, patient enrollment remains challenging in South Korea. We aimed to identify key barriers to clinical trial participation from the perspectives of medical oncologists, patients, and caregivers. MATERIALS AND METHODS: Two web-based surveys were conducted in August 2022: one involving 100 KCSG-affiliated medical oncologists, and another involving 100 cancer patients and 100 caregivers. Structured questionnaires were used to assess experiences, perceived barriers, and access to trial-related information. Focus group interviews (FGIs) were conducted with six patients and caregivers to explore qualitative insights in greater depth. RESULTS: Among oncologists, 98% had prior experience with clinical trials; the same proportion expressed willingness to refer patients to other institutions. However, 76% reported failed or abandoned referral attempts, primarily due to insufficient information on trial eligibility and enrollment status. Although 86% of patients and caregivers were aware of the clinical trial, only 23% had actual participation experience. Physician recommendations emerged as the most influential factor driving participation. Nonetheless, most reported difficulties in accessing reliable trial information, citing unfamiliarity with search tools, complex content, and absence of centralized platforms. The FGI findings supported these results, highlighting the importance of physician guidance and identifying limited access to information as major barriers to enrollment. CONCLUSION: Despite positive attitudes, clinical trial participation remains constrained by fragmented referral systems and inaccessible information. Establishing a coordinated, interinstitutional referral platform and improving user-friendly information delivery may enhance enrollment and promote equitable access to cancer clinical trials in South Korea.
Impact of High Lymph Node Burden on Brain Metastases in Patients Who Achieved Pathological Complete Response after Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer.
Lee SA, Kim KJ, Woen DY … +17 more , Lee SM, Oh K, Lee CE, Park WK, Yoo JW, Shin DS, Ryu JM, Lee SK, Chae BJ, Yu J, Kim SW, Nam SJ, Kim JY, Park YH, Ko EY, Ko ES, Lee JE
Cancer Res Treat · 2025 Jul · PMID 40635453 · Publisher ↗
PURPOSE: This study aims to investigate the clinical characteristics, outcomes, and predictors of brain metastases in HER2-positive advanced breast cancer patients who achieved pathological complete response (pCR) follow...
PURPOSE: This study aims to investigate the clinical characteristics, outcomes, and predictors of brain metastases in HER2-positive advanced breast cancer patients who achieved pathological complete response (pCR) following neoadjuvant chemotherapy (NAC). This research seeks to inform surveillance strategies and optimize management for high-risk subgroups. MATERIALS AND METHODS: A retrospective analysis of 1,757 patients (2008-2022) classified them into pCR (n=914) and non-pCR (n=843) groups post-NAC. Collected data included demographics, clinical features, and metastasis parameters. Survival outcomes and brain metastasis predictors were assessed using Kaplan-Meier curves, Cox models, and logistic regression. RESULTS: Among pCR patients, brain metastases accounted for 54.2% of distant metastases, significantly affecting OS (p<0.001). Median DMFS was shorter for brain metastases (13.4 months) compared to extracranial metastases (31.1 months) in the pCR group (p=0.005). Positive supraclavicular node (SCN) fine needle aspiration (FNA) and clinical N3 (cN3) stage were the strongest predictors of brain metastases (SCN FNA: OR=12.9, p<0.001; cN3: OR=12.1, p<0.001). Multivariable Cox regression analysis revealed that positive SCN FNA and cN3 stage were strong predictors of reduced DMFS (SCN FNA: HR=2.5, 95% CI: 1.3-3.6, p < 0.001; cN3: HR=11.3, 95% CI: 4.9-33.0, p<0.001). CONCLUSION: This study highlights the challenges of brain metastases in HER2-positive pCR patients, emphasizing the need for tailored therapeutic strategies and enhanced surveillance. High lymph node burden prior to NAC is a significant factor in risk assessment. Therefore, it may be advisable to recommend post-surgery surveillance for high-risk patients.
A Phase II Study of Daratumumab in Combination with Bortezomib and Dexamethasone in Patients with Multiple Myeloma Who Received One Prior Line of Therapy (KMM1906).
Yoo KH, Yoon SE, Kang KW … +11 more , Yi JH, Kim MK, Kim HJ, Kim SH, Park JS, Jung SH, Lee JJ, Min CK, Lee JH, Cho D, Kim K
Cancer Res Treat · 2025 Jun · PMID 40610009 · Publisher ↗
PURPOSE: Daratumumab combined with bortezomib and dexamethasone (DVd) has been established as the standard treatment for relapsed/refractory multiple myeloma (MM) based on pivotal phase 3 trials. A subgroup analysis demo...
PURPOSE: Daratumumab combined with bortezomib and dexamethasone (DVd) has been established as the standard treatment for relapsed/refractory multiple myeloma (MM) based on pivotal phase 3 trials. A subgroup analysis demonstrated enhanced efficacy in the second-line setting, although the fixed duration of bortezomib administration remained a limitation. Therefore, we conducted a phase II trial evaluating continuous bortezomib as maintenance in a DVd regimen for second-line treatment. MATERIALS AND METHODS: This phase II study (KCT0004352) enrolled patients with MM receiving second-line DVd therapy: daratumumab (16 mg/kg IV, weekly for cycles 1-3, every 3 weeks for cycles 4-8, every 4 weeks thereafter), bortezomib (1.3 mg/m² SQ, twice weekly for cycles 1-8, biweekly thereafter), and dexamethasone (20 mg IV or PO on treatment days), as in the pivotal trial. After nine cycles, daratumumab and bortezomib were continued until progression or unacceptable toxicity. The primary endpoint was a ≥ very good partial response (VGPR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and minimal residual disease (MRD) negativity assessed by EuroFlow-based next-generation flow in bone marrow. RESULTS: Between June 2020 and 2021, 26 patients (median age 72) from 10 Korean centers were enrolled. All had one prior treatment line; 73% had prior bortezomib, and 69% had prior immunomodulators. At a median follow-up of 25.4 months, 65% discontinued due to progression, death, or withdrawal. VGPR or better was achieved in 65%, with 23% MRD-negative. Median PFS was 21.8 months; OS was not reached. The 24-month OS rate was 69.2%. Grade 3 adverse events included thrombocytopenia and lymphopenia; 31% had serious AEs, and 65% required dose modifications. CONCLUSION: Continuous DVd therapy showed promising efficacy and manageable toxicity as a second-line option.
Detection of HIV RNA after CAR-T Cell Therapy in A Relapsed/refractory Diffuse Large B-cell Lymphoma Patient: Possibility of False Positivity and Clinical Implications.
Yoon SE, Huh K, Kim TY … +3 more , Huh HJ, Kim SJ, Kim WS
Cancer Res Treat · 2025 Jun · PMID 40610008 · Publisher ↗
CAR-T cell therapy using lentiviral vectors can lead to false-positive HIV RNA detection, making distinguishing true infection from vector-related signals challenging. A 64-year-old male with relapsed/refractory DLBCL (R...
CAR-T cell therapy using lentiviral vectors can lead to false-positive HIV RNA detection, making distinguishing true infection from vector-related signals challenging. A 64-year-old male with relapsed/refractory DLBCL (RR-DLBCL) underwent multiple lines of treatment, including R-CHOP, R-ICE, autologous stem cell transplantation (ASCT), and tisagenlecleucel (tisa-cel, Kymriah). Infectious disease screening before CAR-T therapy was negative for HIV. However, four months post-infusion, during evaluation for second-line CAR-T therapy targeted CD20, HIV RNA was detected in Roche Cobas HIV-1 assay targeted dual target, 5'LTR and gag gene (48 copies/mL). Serial testing showed persistent but low-level positivity of HIV RNA. Retrospective analysis of stored serum samples revealed HIV RNA negativity before tisa-cel infusion but positivity post-infusion in Roche Cobas HIV-1 assay. Additional testing using the Alinity m HIV-1 assay (dual target: 5'LTR and pol gene) and the Abbott RealTime HIV-1 assay (single-target: pol gene) confirmed that only the dual-target assay yielded positive results, suggesting lentiviral vector cross-reactivity rather than actual HIV infection. This case underscores the potential for false-positive HIV-1 RNA detection in CAR-T cell treatment recipients due to vector-derived sequences, emphasizing the need for cautious interpretation of HIV-1 testing.
Nivolumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Korean Patients with HER2-Negative, Untreated, Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer: Subgroup Analysis of a Randomized, Multicenter, Double-Blind Phase 3 Trial (ATTRACTION-4).
Kang YK, Ryu MH, Oh DY … +16 more , Oh SC, Rha SY, Lee KW, Chung IJ, Oh SY, Sym SJ, Kang WK, Kim JG, Shim BY, Kim IH, Kim JY, Song EK, Lee HJ, Kang SY, Koo DH, Oh SY
Cancer Res Treat · 2025 Jul · PMID 40610007 · Publisher ↗
PURPOSE: We report the safety and efficacy of nivolumab + chemotherapy for first-line treatment of advanced or recurrent gastric or gastroesophageal junction cancer in the Korean subpopulation of the ATTRACTION-4 clinica...
PURPOSE: We report the safety and efficacy of nivolumab + chemotherapy for first-line treatment of advanced or recurrent gastric or gastroesophageal junction cancer in the Korean subpopulation of the ATTRACTION-4 clinical trial. MATERIALS AND METHODS: ATTRACTION-4 (NCT02746796) was a double-blind, randomized, placebo-controlled clinical trial of patients aged ≥20 years with histologically confirmed unresectable advanced or recurrent gastric or gastroesophageal junction cancer. Patients received nivolumab or placebo, both combined with physician-choice chemotherapy (oxaliplatin plus oral S-1 [tegafur‒gimeracil‒oteracil] [SOX] or oral capecitabine [CAPOX]). RESULTS: Overall, 464 patients were initially screened in Korea and 291 were randomized to nivolumab + chemotherapy (total/SOX/CAPOX: 148/66/82 patients) or placebo + chemotherapy (total/SOX/CAPOX: 143/61/82 patients). Centrally assessed progression-free survival (median: 14.75 vs. 8.34 months; hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.39‒0.73, p<0.0001), overall survival (19.7 vs. 14.9 months; HR 0.78; 95% CI 0.60‒1.02, p=0.0651), overall response rate (54.7% vs. 47.6%), and duration of response (16.03 vs. 9.86 months) favored nivolumab + chemotherapy vs. placebo + chemotherapy. Grade ≥3 treatment-related adverse events (TRAEs) (56.1% vs. 44.1%), and any-grade endocrine (9.5% vs. 4.2%), hepatic (23.0% vs. 14.7%), hypersensitivity and infusion reactions (15.5% vs. 7.0%), renal (4.1% vs. 0.7%), and skin (44.6% vs. 23.1%) TRAEs tended to be more frequent in the nivolumab + chemotherapy group. CONCLUSION: These findings demonstrate the clinical benefit of nivolumab combined with chemotherapy (either SOX or CAPOX) for first-line treatment of gastric cancer/gastroesophageal junction cancer in Korean patients.
HER3 Expression and PIK3CA Mutational Status Predict Pathological Response of Neoadjuvant Therapy in HER2 Positive Breast Cancer Patients.
Xia X, Zong Z, Shen J … +6 more , Zhou L, Lei Y, Li J, Zheng L, Li F, Wang H
Cancer Res Treat · 2025 Jul · PMID 40610006 · Publisher ↗
PURPOSE: The main purpose of this study is to explore the predictive value of HER3 expression level and PIK3CA mutation for the efficacy of neoadjuvant therapy in HER2 positive breast cancer patients. MATERIAL AND METHOD...
PURPOSE: The main purpose of this study is to explore the predictive value of HER3 expression level and PIK3CA mutation for the efficacy of neoadjuvant therapy in HER2 positive breast cancer patients. MATERIAL AND METHODS: The clinicopathological data of HER2 positive non-specific invasive breast cancer patients who received neoadjuvant treatment in the Second Affiliated Hospital of Anhui Medical University from June 2017 to June 2024 were retrospectively analyzed. The correlation between HER3 expression level detected by immunohistochemistry and PIK3CA gene mutation detected by ARMS-PCR and pathological complete response rate (pCR) was analyzed. RESULTS: Among 51 patients, 29 (56.86%) had positive HER3 expression, 15 (29.41%) had PIK3CA mutation, and 19 (37.25%) had pCR. The expression level of HER3 was correlated with the pCR rate (χ2=7.905, p=0.019). The PIK3CA mutation status was not correlated with the pCR rate (χ2=0.140, p=0.708). The HER3 expression level combined with PIK3CA mutation status affected the pCR rate (p=0.036). Multivariable regression further identified HER3 positivity as an independent negative predictor of pCR (OR=0.08, 95% CI: 0.01-0.50, p=0.008), underscoring its role in therapeutic resistance. CONCLUSION: HER3 expression may serve as a critical biomarker for guiding therapeutic strategies in HER2-positive breast cancer patients. The combinatorial effect of HER3 overexpression and PIK3CA mutations may exacerbate therapeutic resistance, while dual-targeted strategies against the HER3/PI3K pathway could potentially improve clinical outcomes in treatment-resistant populations.
Anticancer Treatment Influences TREM2 in Tumor-Associated Macrophages in Lung Cancer.
Cha YJ, Lee EH, Kim CY … +5 more , Choi YJ, Park MK, Lee SH, Kim EY, Chang YS
Cancer Res Treat · 2026 Apr · PMID 40575951 · Full text
PURPOSE: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well establish...
PURPOSE: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME. MATERIALS AND METHODS: Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them. RESULTS: Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. CONCLUSION: Given TREM2's central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.
Uncovering Putative Causal Non-coding RNAs in Acute and Chronic Myeloid Leukemia: A Genome-Wide Mendelian Randomization Study.
Jung S, Kim JW, Han B
Cancer Res Treat · 2026 Apr · PMID 40575950 · Full text
PURPOSE: Although non-coding RNAs (ncRNAs) have often been implicated in various cancers, their causal roles in acute (AML) and chronic myeloid leukemia (CML) remain unclear. Here, we conducted a genome-wide two-sample M...
PURPOSE: Although non-coding RNAs (ncRNAs) have often been implicated in various cancers, their causal roles in acute (AML) and chronic myeloid leukemia (CML) remain unclear. Here, we conducted a genome-wide two-sample Mendelian randomization (MR) study to investigate the causal effects of a comprehensive set of ncRNAs on AML and CML. MATERIALS AND METHODS: We used summary statistics of blood expression quantitative trait loci (eQTL) from the eQTLGen consortium (31,684 European participants) as exposure data. Genome-wide association study summary statistics from the FinnGen study (AML, 322 cases; CML, 303 cases) and UK Biobank (UKBB) (AML, 318 cases; CML, 153 cases) served as outcome data. The generalized inverse-variance weighted (GIVW) method was used as the primary MR method. Two additional MR methods (generalized MR-Egger and weighted median), sensitivity analyses, and the HEIDI test were further employed to support our findings. RESULTS: Upregulated HCG22 and RP11-42I10.1 were causally linked to increased AML risk, while the GMDS-AS1 locus was positively associated with increased CML risk. We highlight these ncRNAs for their consistent significance across all three MR methods, with no evidence of bias in sensitivity analyses (F-test, Cochran's Q-test, MR-Egger intercept, MR-PRESSO global test) and no indication of confounding from the HEIDI test. These findings were primarily discovered in FinnGen (FDRGIVW < 0.05), their significance was validated in UKBB (pGIVW < 0.05). Upon validation with an independent linkage disequilibrium reference panel, they remained robust. CONCLUSION: This study provides evidence of causal relationships between ncRNAs and the subtypes of AML and CML, notably highlighting HCG22 and RP11-42I10.1 in AML and the GMDS-AS1 locus in CML.
Insomnia, Pain, and Pain-Related Dysfunctional Beliefs about Sleep among Patients with Cancer.
Chung S, Lee S, Shahrier MA … +1 more , Jeon S
Cancer Res Treat · 2026 Apr · PMID 40575949 · Full text
PURPOSE: We explored the reliability and validity of the Pain-related Beliefs and Attitudes about Sleep (PBAS) scale among patients with cancer. Further, we compared the usability of the PBAS scale with that of the Cance...
PURPOSE: We explored the reliability and validity of the Pain-related Beliefs and Attitudes about Sleep (PBAS) scale among patients with cancer. Further, we compared the usability of the PBAS scale with that of the Cancer-related Dysfunctional Beliefs and Attitudes about Sleep-14 (C-DBAS-14) among patients with cancer. MATERIALS AND METHODS: The medical records of 252 patients with cancer who visited the sleep clinic from August 1, 2023 to June 30, 2024 were retrospectively analyzed. The responses of the enrolled patients to the PBAS, C-DBAS-14, Insomnia Severity Index (ISI), and Numeric Rating Scale of pain were collected. RESULTS: The internal consistency reliability of the PBAS scale was excellent (Cronbach's alpha of 0.96). Confirmatory factor analysis showed that the two-factor structure of the PBAS for patients with cancer is a good fit for the model (Comparative Fit Index, 0.99; Tucker-Lewis Index, 0.99; root mean square error of approximation, 0.14; standardized root mean square residual, 0.05). The convergent validity of the Korean version of the PBAS in patients with cancer was good, as indicated by its significant association with pain severity (r=0.63, p < 0.001), C-DBAS-14 (r=0.33, p < 0.001), and ISI (r=0.21, p < 0.01). The PBAS adequately reflected an increase in pain severity and was more effective and appropriate for capturing pain-related dysfunctional sleep beliefs than the C-DBAS-14. CONCLUSION: The Korean version of the PBAS showed high reliability and validity in patients with cancer, and applicability across cancer types and cancer-related beliefs.
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