Cancer Res Treat [JOURNAL]
Sun
200 papers
Clinical Outcomes and Histologic Subtype-Specific Patterns in Oligometastatic Soft Tissue Sarcoma of the Extremities and Trunk Wall: Implications for Curative Local Ablative Therapy.
Yang E, Kim HS, Park JH … +7 more , Kim Y, Kim S, Kim M, Youk J, Kim HJ, Kang HC, Han I
Cancer Res Treat · 2025 Oct · PMID 41166925 · Publisher ↗
PURPOSE: Oligometastatic soft tissue sarcoma (STS) may offer the possibility of cure compared with polymetastatic disease, with progression patterns and treatment responses varying across histologic subtypes. This study...
PURPOSE: Oligometastatic soft tissue sarcoma (STS) may offer the possibility of cure compared with polymetastatic disease, with progression patterns and treatment responses varying across histologic subtypes. This study investigated the clinical characteristics, oncologic outcomes, and histologic subtype-specific features of oligometastatic STS. MATERIALS AND METHODS: We reviewed records of 1,243 patients with extremity/trunk STS who underwent curative surgery between 2000 and 2023. Oligometastatic recurrence occurred in 170 (13.6%), 149 of whom received local ablative therapy (LAT). Disease-specific survival (DSS) and progression-free survival (PFS) were analyzed, along with prognostic factors and subtype-specific characteristics. RESULTS: The median follow-up was 52.5 months. Surgery alone was the most common LAT (71.2%), followed by surgery with radiotherapy, radiotherapy alone and radiofrequency ablation. The median DSS was 50.0 months (95% confidence interval [CI], 31.5-68.5), with a 5-year DSS rate of 45.2%. The median PFS was 12.0 months (95% CI, 7.6-16.4), with a 5-year PFS of 28.1%. On multivariate analysis, LAT was independently associated with longer DSS (hazard ratio [HR], 9.629; p<0.001). Smaller oligometastatic lesion size and adequate local control of the primary tumor were also independently associated with longer DSS. Metastasis-free interval > 6 months independently predicted longer PFS. Histologic subtypes demonstrated distinct clinical behaviors; for example, myxofibrosarcoma had a lower metastatic rate but poorer DSS, whereas synovial sarcoma showed relatively favorable long-term survival. CONCLUSION: Oligometastatic STS represents an intermediate disease state in which LAT can provide meaningful survival benefit. Subtype-specific differences in metastatic behavior and survival outcomes would support individualized, multimodal, and potentially curative treatment strategies.
Trajectory of Lymph Node Metastasis Reflects the Molecular Features of Esophageal Squamous Cell Carcinoma.
Park J, Park SY, Kim HE … +4 more , Jo SY, Won J, Kim DJ, Kim S
Cancer Res Treat · 2025 Oct · PMID 41132042 · Publisher ↗
PURPOSE: Esophageal squamous cell carcinoma (ESCC) is frequently accompanied by lymph node metastasis (LNM) to the neck, chest, and abdomen. Despite its significance as a key prognostic factor, the genomic trajectory of...
PURPOSE: Esophageal squamous cell carcinoma (ESCC) is frequently accompanied by lymph node metastasis (LNM) to the neck, chest, and abdomen. Despite its significance as a key prognostic factor, the genomic trajectory of LNM remains poorly understood. This study aimed to characterize the underlying patterns and genomic characteristics of LNM. MATERIALS AND METHODS: Whole-exome sequencing and transcriptome sequencing were performed on 45 multiregional samples (10 primary tumors, 10 normal esophageal tissues, and 25 lymph node tumors) from 10 ESCC patients who underwent esophagectomy with three-field lymphadenectomy. The temporal trajectory of metastasis was reconstructed through phylogenetic analysis, leveraging somatic mutations identified in the primary tumor and lymph nodes. RESULTS: Somatic mutations preceding metastasis included major driver mutations, such as TP53 and KMT2D, and displayed a mutational process associated with alcohol consumption (SBS16), emphasizing its influence on early tumorigenesis. In contrast, post-lymph node metastatic mutations were sporadic. Lymph nodes seeded later acquired mutations at a faster rate, suggesting increased genomic instability. In three of nine patients (33%), nodal skip metastasis (NSM) was observed, including two cases detected exclusively via genomic analysis, highlighting the necessity of phylogenetic assessment to avoid misclassification. Transcriptome analysis revealed activation of epithelial-mesenchymal transition and KRAS signaling pathways in NSM tumors, indicative of poor prognostic outcomes. CONCLUSION: Our study provides a molecular understanding of LNM, emphasizes the potential importance of node-skipping patterns in ESCC, and underscores the utility of genomic analysis in elucidating the connection between LNM.
Disease Burden and Treatment Pattern of Advanced or Recurrent Endometrial Cancer in Korea: A Nationwide Database (DIRECTION) Study.
Cho HW, Kim SI, Bae MJ … +5 more , Kwon KE, Jung C, Lee Y, Ahn J, Kim K
Cancer Res Treat · 2025 Oct · PMID 41132041 · Publisher ↗
PURPOSE: Advanced/recurrent endometrial cancer (EC) patients has a poor prognosis, with higher recurrence and mortality than early-stage. However, as the real-world disease burden in these patients remains unclear, we ai...
PURPOSE: Advanced/recurrent endometrial cancer (EC) patients has a poor prognosis, with higher recurrence and mortality than early-stage. However, as the real-world disease burden in these patients remains unclear, we aimed to investigate systemic anticancer therapy (SACT) patterns, healthcare resource utilization (HCRU), and costs in advanced/recurrent EC patients. MATERIALS AND METHODS: This nationwide population-based study used Korean claims data from 2008 to 2022. Adult patients with advanced/recurrent EC who received first-line SACT were included. For advanced EC, first-line SACT was defined as the initial therapy following EC diagnosis, while for recurrent EC it was defined as the initial therapy after recurrence following completion of primary therapy. We analyzed SACT patterns, prognosis, all cause- and EC-related HCRU, and costs. RESULTS: A total of 2,704 EC patients were included. The most commonly used SACT was platinum-based regimen. From the first to third line, median values of SACT-free interval (18.40, 5.03, and 3.22 months) and time to next treatment (TTNT, 25.43, 9.27 and 6.44 months) showed decreasing trends. All-cause/EC-related HCRU and costs were increased with SACT progression; all-cause inpatient visits and total costs increased from 0.58 to 1.04 times per-patient-per-month (PPPM) and from $1,197.96 to $2,354.37 USD PPPM. CONCLUSION: This study demonstrated significant variability in SACT regimen sequence, highlighting the lack of consensus on standard treatment after disease relapse. Shorter TTNT and SACT-free intervals and higher HCRU and costs in later lines indicate worsening prognosis and increasing disease burden. These findings suggest the urgent need for more effective treatments, including new therapeutic agents, to address the unmet clinical needs of advanced/recurrent EC patients.
WNT3A Upregulates the RIP1/HIF-1α/GDF-15 Pathway to Induce EMT and Thereby Increase Colorectal Cancer Cell Migration and Invasion.
Kang AR, Kim TJ, Yoo JY … +3 more , Hwang SG, Song JY, Park JK
Cancer Res Treat · 2025 Oct · PMID 41132040 · Publisher ↗
PURPOSE: We previously demonstrated that WNT signaling, a key regulator of epithelial-mesenchymal transition (EMT), promotes malignancy via RIP1 in colorectal cancer (CRC). In this study, we aimed to reveal the novel sig...
PURPOSE: We previously demonstrated that WNT signaling, a key regulator of epithelial-mesenchymal transition (EMT), promotes malignancy via RIP1 in colorectal cancer (CRC). In this study, we aimed to reveal the novel signaling pathway through which WNT3A induces EMT in CRC. MATERIALS AND METHODS: CRC cells (DLD-1, HCT116) and mouse embryonic fibroblasts (MEFs; wtMEF and RIP1-/- MEF) were used in this study. Expression levels of GDF-15 and GFRAL were assessed by RT-qPCR, immunoblotting, and ELISA. RIP1 and HIF-1α were silenced using siRNA or shRNA. Cytokine profiling and ELISA were performed to quantify GDF-15 secretion. Migration and invasion assays were conducted in GDF-15-treated cells. Expression of HIF-1α within the pathway was analyzed with RT-qPCR and immunoblotting. In vivo expressions of GDF-15 and GFRAL were detected in human blood and CRC tissue specimens. RESULTS: WNT3A treatment significantly upregulated both mRNA and protein levels of GDF-15 and GFRAL in CRC cells. Silencing of RIP1 with siRIP1 or shRIP1 decreased the expression and secretion of GDF-15 and GFRAL. Cytokine profiling and ELISA confirmed that RIP1 facilitates GDF-15 secretion. Treatment with GDF-15 led to enhanced cell migration, invasion, and increased EMT marker expression. We also detected increases of GDF-15 in blood specimens and metastatic tissues of CRC patients. Furthermore, HIF-1α was identified as a key transcription factor downstream of RIP1 that regulates GDF-15 expression. CONCLUSION: Our findings demonstrate that the novel WNT3A/RIP1/HIF-1α/GDF-15 signaling axis induces EMT, migration, and invasion in CRC. This pathway might represent a potential therapeutic target for limiting metastatic progression in CRC.
Prognostic Impact of Organ-Specific Metastasis in Non-Small-Cell Lung Cancer.
Ryu WK, Ganbaatar M, Park N … +4 more , Lee HY, Kim HC, Ryu JS, Lim JH
Cancer Res Treat · 2025 Oct · PMID 41084178 · Publisher ↗
PURPOSE: Prognostic stratification is essential in non-small-cell lung cancer (NSCLC) to guide treatment decisions. While the TNM staging system has evolved to refine the M category based on metastatic burden, it does no...
PURPOSE: Prognostic stratification is essential in non-small-cell lung cancer (NSCLC) to guide treatment decisions. While the TNM staging system has evolved to refine the M category based on metastatic burden, it does not account for differences in prognosis based on the specific organ affected. This study evaluates whether incorporating organ-specific metastasis improves prognostic discrimination in stage IV NSCLC. MATERIALS AND METHODS: We conducted a retrospective cohort study using data from the Korean Central Cancer Registry (2014-2018). Patients with stage IV NSCLC were classified according to the 9th edition TNM classification: M1b (single-organ, single metastasis), M1c1 (multiple metastases within a single organ), and M1c2 (multiple organ metastases). Survival outcomes were compared across groups using Kaplan-Meier analysis and Cox proportional hazards modeling. RESULTS: Among 3,165 patients, 56.5% had single-organ metastases, while 43.5% had multiple organ metastases. Median overall survival (OS) was longest in M1b (8.0 months), followed by M1c1 (6.0 months), and shortest in M1c2 (5.9 months) (p<0.001). However, survival varied by metastatic organ. Liver, adrenal, and uncommon-site metastases were associated with significantly worse OS, even among M1b patients. Some M1b and M1c1 patients with high-risk organ metastases had worse survival than M1c2 patients, challenging the TNM-defined prognostic hierarchy. CONCLUSION: The current TNM M category does not fully capture the prognostic impact of metastatic organ involvement. Incorporating organ-specific metastases into staging and prognostic models could refine risk stratification and improve personalized treatment approaches for stage IV NSCLC.
Excess Cholesterol Biosynthesis by Up-Regulated HMGCS1 in Colorectal Cancer Cells Induced M2-Like Tumor-Associated Macrophage Polarization Via Extracellular Vesicles.
Yang L, Wu B, Sun T … +5 more , Sun H, Ma J, Liu X, Zhou D, Yang S
Cancer Res Treat · 2025 Oct · PMID 41084177 · Publisher ↗
PURPOSE: The aetiology of colorectal cancer (CRC) is attributed to the intrinsic malignant cell transformation and the extrinsic tumor microenvironment (TME). Within the TME, M2-like tumor-associated macrophages (TAMs) p...
PURPOSE: The aetiology of colorectal cancer (CRC) is attributed to the intrinsic malignant cell transformation and the extrinsic tumor microenvironment (TME). Within the TME, M2-like tumor-associated macrophages (TAMs) play a pivotal role in promoting CRC malignancy. Although the interaction between tumor cells and TAMs has been studied, the mechanism underlying the polarization of M2-like TAMs directed by CRC cells remains unclear. MATERIALS AND METHODS: Macrophage polarization was analyzed by flow cytometry. Cytokine production was quantified by qPCR. EVs were identified by transmission electron microscopy and western blotting. CRC cell apoptosis and viability were measured by flow cytometry and CCK8 assay, respectively. RESULTS: The results showed that CRC cells have high expression of HMGCS1, the enzyme responsible for catalyzing the synthesis of HMG-CoA during cholesterol biosynthesis. The increased expression of HMGCS1 resulted in an excess of cholesterol in CRC patients. The excess cholesterol derived from CRC cells was released via extracellular vesicles (EVs) and taken up by surrounding macrophages via the CD36 receptor. Macrophages that took up CRC cell-derived cholesterol showed a preferential polarization towards M2-like TAMs, which produced large amounts of pro-tumor cytokines. The production of these cytokines further accelerated the progression of the surrounding CRC. CONCLUSION: Our findings revealed a mutual stimulatory effect between CRC cells and M2-like TAMs. CRC cells with hyper-expressed HMGCS1 facilitated M2-like TAM polarization by releasing cholesterol-rich EVs, and M2-like TAMs in turn promoted CRC malignancy. These findings suggest that inhibiting excessive cholesterol production may be a promising strategy for the treatment of advanced CRC.
Real World Efficacy of 1st-Line Nivolumab Plus Ipilimumab and its Practical Predictive Biomarkers in Advanced Renal Cell Carcinoma: First Analysis from RENOIR Study (KCSG GU22-13).
Kim JH, Shin SJ, Bae WK … +18 more , Kim SH, Kim JY, Im HS, Kim IH, Kim IH, Park K, Kim EJ, Choi M, Lim JH, Kim H, Lee K, Kim HJ, Jo J, Lee HJ, Kim D, Sohn BS, Park I, Park JH
Cancer Res Treat · 2025 Oct · PMID 41084176 · Publisher ↗
PURPOSE: We investigated the real-world efficacy of first-line nivolumab plus ipilimumab (NI) and its predictive clinicopathological biomarkers in patients with advanced renal cell carcinoma(aRCC). MATERIALS AND METHODS:...
PURPOSE: We investigated the real-world efficacy of first-line nivolumab plus ipilimumab (NI) and its predictive clinicopathological biomarkers in patients with advanced renal cell carcinoma(aRCC). MATERIALS AND METHODS: We retrospectively analyzed 466 patients with aRCC who started first-line NI between 2019 and 2023 at 21 Korean tertiary hospitals. The primary outcome was objective response rate (ORR). Secondary outcomes were duration of response (DoR), progression-free survival (PFS), overall survival (OS), and identification of practical clinicopathological biomarkers. RESULTS: Median age of patients was 65 years, and 77.7% were male. ORR was 44.8% including 5.2% of complete response, and median DoR was 39.8 months. Male sex and lung metastasis were predictive markers of objective response, and achieving complete response was significantly associated with a longer DoR (p=0.03). With a median follow-up duration of 23.7 months, the median PFS and OS were 11.5 and 44.2 months, respectively. Full exposure to four cycles of ipilimumab was significantly associated with better PFS and OS. Durable response could significantly predict better OS, whereas multiple metastatic sites (≥4) and poor IMDC risk were two independent predictors for inferior OS. Among the 50 patients who completed 2 years of NI treatment, continuation of nivolumab beyond 2 years has marginally improved OS (p=0.09). CONCLUSION: First-line NI showed comparable and competent efficacy in Korean patients with aRCC. We suggest completing full exposure to ipilimumab and durable response as practical predictors of enriched benefits of NI in our real-world.
Impact of Occupational Lead Exposure on Lung Cancer Risk in Korean Male Workers: A Retrospective Cohort Study.
Lee KE, Lee S, Yoon JH … +1 more , Ye S
Cancer Res Treat · 2025 Oct · PMID 41035215 · Publisher ↗
PURPOSE: In 2006, the IARC reported that inorganic lead is carcinogenic in animals but with limited evidence in humans. In addition, some studies have reported that exposure to lead increases the risk of lung cancer, but...
PURPOSE: In 2006, the IARC reported that inorganic lead is carcinogenic in animals but with limited evidence in humans. In addition, some studies have reported that exposure to lead increases the risk of lung cancer, but this remains controversial. Therefore, we aimed to assess the risk of developing lung cancer according to blood lead levels in workers with occupational lead exposure. MATERIALS AND METHODS: A retrospective cohort study of male workers with 2009 blood lead (PbB) concentrations was conducted using nationwide special health examination data (SHED) from 2009 to 2021 and cancer registry data from 1999 to 2020 from the Republic of Korea. Standardized incidence ratios (SIRs) for lung cancer risk at each PbB level were calculated with a five-year wash-out period, adjusting for age, smoking status, duration of exposure, and the number of co-exposures to lung carcinogens. RESULTS: The study included 26,092 workers with an average follow-up period of 9.98 years. Compared with workers with PbB levels <3.130 µg/dL, the adjusted SIRs for lung cancer risk were 2.95 (95% confidence interval [CI]: 1.47-5.27) and 3.13 (95% CI: 1.82-5.00) for workers with PbB levels of 3.130-4.899 and ≥4.900 µg/dL, respectively, indicating a significant dose-response trend. CONCLUSION: This study demonstrates a significant association between lead exposure and an increased risk of lung cancer, highlighting the need for stronger occupational health policies and ongoing monitoring of workers exposed to lead. The observed dose-response relationship underscores the importance of reassessing current occupational safety standards and strengthening measures to reduce lead exposure in the workplace.
Effects of Exercise Interventions on Breast Cancer Patients During Adjuvant Therapy: A Systematic Review and Meta-Analysis.
Sun Z, Han T, Feng L … +4 more , Mao D, Zhao C, Han J, Shang Q
Cancer Res Treat · 2025 Oct · PMID 41035214 · Publisher ↗
PURPOSE: Exercise can enhance the therapeutic effects of adjuvant medications, improve both physiological and psychological functions, and increase physical fitness among breast cancer patients receiving adjuvant therapy...
PURPOSE: Exercise can enhance the therapeutic effects of adjuvant medications, improve both physiological and psychological functions, and increase physical fitness among breast cancer patients receiving adjuvant therapy. This systematic review and meta-analysis examined the latest research on the effects of exercise interventions in this population. Furthermore, subgroup analyses were performed based on exercise type, intensity, frequency, duration and Types of adjuvant therapy. MATERIALS AND METHODS: The PubMed, Embase, CINAHL, and CENTRAL databases were systematically searched from inception to April 2024 to identify randomized controlled trials (RCTs) examining the use of exercise interventions among breast cancer patients receiving adjuvant therapy. The data extracted from the included studies were analyzed via RevMan 5.4. RESULTS: A total of 34 studies involving 2,696 participants were included, with 1,369 in the intervention group and 1,327 in the control group, and a mean age ranging from 40 to 60 years. Compared to the control group, exercise interventions improved fatigue, muscular strength, cardiorespiratory fitness, inflammation, and quality of life in breast cancer patients (fatigue: SMD=-0.29, 95% CI (-0.50, 0.09), p=0.005; upper limb strength: SMD=0.50, 95% CI (0.33, 0.68), p<0.00001, lower limb strength: SMD=0.37, 95% CI (0.22, 0.52), p<0.0001; cardiorespiratory fitness: SMD =0.51, 95% CI (0.26,0.75), p<0. 0001; inflammation: SMD =-0.36, 95% CI (-0.66, -0.06), p=0.02; quality of life: SMD=0.21, 95% CI (0.11, 0.31), p< 0.0001). Moderate effect sizes were observed for the alleviation of anxiety and depressive symptoms, although these results did not reach statistical significance (depression: SMD=-0.13, 95% CI (-0.28, 0.02), p=0.08; anxiety: SMD=-0.81, 95% CI (-1.65, 0.03), p=0.06). This meta-analysis was registered in Prospero, the international register of systematic reviews, with registration number: CRD42024553589. CONCLUSION: Exercise during adjuvant therapy can reduce the side effects of adjuvant medications, improve both physiological and psychological functions, and enhance physical fitness among patients with breast cancer.
LRRC15 Promotes the Development of Breast Cancer by Regulating Autophagy through the PI3K/AKT/mTOR Signaling Pathway.
Fan X, Gao L, Zhang Z … +7 more , Jiang X, Wang X, Shi J, Ling Y, Yan R, Shi J, Yu L
Cancer Res Treat · 2025 Sep · PMID 40997932 · Publisher ↗
PURPOSE: Leucine-rich repeats (LRR) play important roles in tumorigenesis and may serve as novel biomarkers for cancer therapy. The expression of leucine-rich repeat-containing protein 15 (LRRC15) is increased in several...
PURPOSE: Leucine-rich repeats (LRR) play important roles in tumorigenesis and may serve as novel biomarkers for cancer therapy. The expression of leucine-rich repeat-containing protein 15 (LRRC15) is increased in several cancers. However, it is still unknown whether LRRC15 is involved in breast cancer and autophagy. MATERIALS AND METHODS: This study conducted bioinformatic analysis on LRRC15 expression and prognosis in breast cancer. Clinical samples were collected and subjected to immunohistochemistry and qRT-PCR to analyze LRRC15 expression in tissues and serum. Clonal formation, MTT, wound healing, and Transwell assays were used to examined breast cancer cell proliferation, migration, and invasion. Western blotting detected autophagy-related and PI3K/AKT/mTOR signaling pathway proteins. RESULTS: Patients with breast cancer having elevated expression of LRRC15 have a markedly worse prognosis compared with those having lower levels. Furthermore, LRRC15 expression was strongly correlated with tumor aggressiveness and poor differentiation in breast cancer cell lines. Functionally, LRRC15 drives cancer cell proliferation, migration, and invasion. LRRC15 inhibited autophagy in breast cancer cells, thus modulating their proliferative capacity. Mechanistically, LRRC15 exerted these effects by activating the PI3K/AKT/mTOR signaling cascade. CONCLUSION: LRRC15 regulates autophagy-induced proliferation and other biological activities of breast cancer cells through the PI3K/AKT/mTOR signaling pathway.
Extracellular Vesicle-Derived Adenosine as a Diagnostic Metabolic Biomarker for Pancreatic Ductal Adenocarcinoma.
Xia T, Ouyang W, Wang J … +5 more , Wang J, Mou Y, Yang Z, Fang H, Gui S
Cancer Res Treat · 2025 Sep · PMID 40997931 · Publisher ↗
PURPOSE: Current non-invasive diagnostic tools for pancreatic ductal adenocarcinoma (PDAC) exhibit limited sensitivity and specificity. This study aimed to identify more accurate plasma biomarkers by profiling extracellu...
PURPOSE: Current non-invasive diagnostic tools for pancreatic ductal adenocarcinoma (PDAC) exhibit limited sensitivity and specificity. This study aimed to identify more accurate plasma biomarkers by profiling extracellular vesicles (EVs), which are enriched in tumor-derived metabolites and proteins. MATERIALS AND METHODS: Plasma samples were collected under strict fasting and standardized processing protocols from patients diagnosed with PDAC, chronic pancreatitis (CP), and tumor-free controls (Ctrl). EVs were isolated from these plasma samples and subjected to comprehensive metabolomic and proteomic profiling to identify disease-specific biomarkers. RESULTS: A biomarker panel comprising adenosine, adenine, and N-acetylneuraminate (AAN) demonstrated outstanding diagnostic performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.968 (95% CI: 0.92-1.00). At a fixed specificity of 96.8%, the panel yielded a sensitivity of 95.0% (95% CI: 85.0%-100.0%), significantly reducing the classification error from 30% with CA19-9 to 5% with the AAN panel. Among individual markers, adenosine alone showed high diagnostic power (AUC=0.952), correlating with increased expression of 5'-nucleotidase ecto (NT5E), indicative of elevated extracellular purine metabolism. Importantly, these features were unique to the EV compartment and outperformed markers derived from total plasma metabolite profiles. CONCLUSION: The integration of EV metabolomics and proteomics revealed enhanced purine metabolism, particularly elevated extracellular adenosine, as a distinctive hallmark of PDAC. EV-derived adenosine emerges as a highly promising non-invasive biomarker with superior diagnostic accuracy compared to CA19-9.
IFITM1 Influences Natural Killer Cell-Mediated Cytotoxicity by Modulation of HLA class I Expression in Triple-Negative Breast Cancer Cells.
Lee H, Park C, Kang K … +7 more , Hong SA, Cho G, Cheon I, Ahn YH, Yoon JS, Ko YH, Won HS
Cancer Res Treat · 2025 Sep · PMID 40997930 · Publisher ↗
PURPOSE: Interferon-induced transmembrane protein 1 (IFITM1) is associated with a poor prognosis in triple-negative breast cancer (TNBC); however, the mechanisms by which IFITM1 contributes to oncogenesis in TNBC are unc...
PURPOSE: Interferon-induced transmembrane protein 1 (IFITM1) is associated with a poor prognosis in triple-negative breast cancer (TNBC); however, the mechanisms by which IFITM1 contributes to oncogenesis in TNBC are unclear. MATERIALS AND METHODS: We established two stable cell lines: IFITM1-overexpressing cell line (MB-231-IFITM1-OE) and IFITM1 knockdown cell line (BT-20-IFITM1-KD). The transcriptional activity of β-catenin and the cytotoxic activity of natural killer (NK) cells were evaluated using the luciferase assay and the lactate dehydrogenase cytotoxicity assay. The expression of IFITM1, β-catenin, and HLA class I was assessed by immunohistochemistry in patients with TNBC. RESULTS: Knockdown of IFITM1 in BT-20 cells reduced cell proliferation and ectopically expressed IFITM1 in MB-231 cells increased cell proliferation. RNA sequencing analysis revealed that IFITM1 expression positively correlated with the Wnt/β-catenin signaling pathway and NK cell-mediated cytotoxicity. MB-231-IFITM1-OE cells showed increased β-catenin transcriptional activity and NK cell cytotoxic activity compared with controls, while transient knockdown of IFITM1 in MB-231-IFITM1-OE cells led to a decrease in β-catenin transcriptional activity and NK cell cytotoxic activity. MB-231-IFITM1-OE cells exhibited decreased HLA class I expression, which may have contributed to their increased susceptibility to NK cell-mediated lysis. β-catenin or JAK inhibitor reduced NK cell-mediated cytotoxicity via upregulation of HLA class I. Patients with IFITM1 overexpression showed a trend toward increased β-catenin positivity and HLA class I negativity. CONCLUSION: IFITM1 overexpression was associated with Wnt/β-catenin signaling and NK cell-mediated cytotoxicity via downregulation of HLA class I in TNBC cells, suggesting that IFITM1 might have immunoregulatory effects on the tumor microenvironment.
Effectiveness of CAR-T Cell Therapies for Relapsed/Refractory Follicular Lymphoma: An External Control Arm Study.
Seo HJ, Kim JH, Yoon SE … +4 more , Kim WS, Yon DK, Shin JY, Kim SJ
Cancer Res Treat · 2025 Sep · PMID 40968610 · Publisher ↗
PURPOSE: Axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabactagene maraleucel (liso-cel) have received regulatory approval for relapsed or refractory follicular lymphoma (r/r FL). However, the d...
PURPOSE: Axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabactagene maraleucel (liso-cel) have received regulatory approval for relapsed or refractory follicular lymphoma (r/r FL). However, the data are scare on their comparative effectiveness against the salvage therapies available in real-world settings. This study aimed to indirectly compare treatment outcomes of axi-cel, tisa-cel, and liso-cel versus usual care in South Korean patients with FL. MATERIALS AND METHODS: To assess effectiveness in real-world data, aggregate data from the ZUMA-5, ELARA, and TRANSCEND FL studies were compared with individual patient data from the Samsung Medical Center - Lymphoma Cohort Study (SMC-LCS). Patients meeting ZUMA-5, ELARA, and TRANSCEND FL eligibility criteria were selected as the external control arm. All eligible treatment lines per patient were analyzed as independent episodes and weighted using the matching-adjusted indirect comparison (MAIC) method. Time-to-event outcomes were assessed with weighted Kaplan-Meier analysis, and adjusted hazard ratios (aHR) were estimated using Cox proportional hazards models. RESULTS: Axi-cel included 127 patients, tisa-cel included 94, liso-cel included 101, and 121 episodes from 49 patients were analyzed in the external control arm. The weighted hazard ratios for overall survival (OS) and progression-free survival (PFS) for axi-cel versus the external control were 0.37 (95% CI, 0.21-0.64), 0.35 (95% CI, 0.20-0.59), respectively. For tisa-cel, the HRs were 0.24 (95% CI, 0.11-0.53), and 0.35 (95% CI, 0.20-0.60), respectively. For liso-cel, the HRs were 0.38 (95% CI, 0.13-1.04), and 0.36 (95% CI, 0.15-0.88), respectively. CONCLUSION: All three CAR-T therapies showed outstanding effectiveness compared to conventional treatments in usual care in South Korea.
Fraction of Cancer Attributable to Occupational Carcinogens in Korea between 2015 and 2030.
Kim EM, Koh DH, Sung S … +12 more , Hong Y, Moon S, Lee JE, Ko KP, Park SK, Min J, Choi S, Park JH, Lee SG, Kim HC, Park DU, Kim I
Cancer Res Treat · 2025 Sep · PMID 40968609 · Publisher ↗
PURPOSE: To estimate the contribution of occupational carcinogens to cancer incidence and mortality in the Korean population between 2015 and 2030. MATERIALS AND METHODS: We selected occupational carcinogens classified a...
PURPOSE: To estimate the contribution of occupational carcinogens to cancer incidence and mortality in the Korean population between 2015 and 2030. MATERIALS AND METHODS: We selected occupational carcinogens classified as International Agency for Research on Cancer (IARC) Group 1 and estimated the prevalence of exposure using data from the Korean CARcinogen EXposure (K-CAREX) and previous studies. Relative risks were calculated using published literature through a meta-analysis. Levin's formula was used to estimate population attributable fraction (PAF) while considering a 15-year latency period between exposure, cancer incidence, and death. Additionally, trends in cancer PAF were calculated up to 2030, assuming constant relative risks and a 15-year latency period. RESULTS: In 2015, the PAFs for occupational carcinogen-related cancer incidence and mortality were 1.00% (men: 1.75%, women: 0.15%) and 1.97% (men: 2.97%, women: 0.33%), respectively, with asbestos being the largest contributor (incidence: 0.48%; mortality: 0.98%). In 2030, the PAFs for occupational carcinogen-related cancer incidence and mortality were 0.34% (men: 0.62%, women: 0.07%) and 0.80% (men: 1.22%; women: 0.15%), respectively, with diesel engine exhaust being projected to become the largest contributor by 2030 (incidence: 0.16%, mortality: 0.41%). CONCLUSION: The PAFs of occupational carcinogens in Korea between 2015 and 2030 were estimated to be very low in the general population, and the values are expected to decrease over time owing to various regulations to prevent exposure to occupational carcinogens. Therefore, while regulating well-known occupational carcinogens, efforts should be made to monitor newly identified ones to ensure prompt implementation of preventive measures.
LncRNA DGUOK-AS1 Promotes Bladder Cancer Progression by Enhancing EFTUD2 Stability.
Ying W, Li D, Feng N … +1 more , Wei W
Cancer Res Treat · 2025 Sep · PMID 40968608 · Publisher ↗
PURPOSE: Long noncoding RNAs (lncRNAs) are increasingly being recognized to play important roles in cancer pathogenesis. However, the functional mechanisms of most lncRNAs remain poorly understood. MATERIALS AND METHODS:...
PURPOSE: Long noncoding RNAs (lncRNAs) are increasingly being recognized to play important roles in cancer pathogenesis. However, the functional mechanisms of most lncRNAs remain poorly understood. MATERIALS AND METHODS: RNA sequencing was performed to identify differentially expressed lncRNAs between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). In vitro and in vivo assays were conducted to investigate the functional role of lncRNA deoxyguanosine kinase 1 antisense RNA 1 (DGUOK-AS1). Meanwhile, RNA pull-down, RNA immunoprecipitation, co-immunoprecipitation, Western blot, and reverse transcription quantitative polymerase chain reaction assays were performed to explore the potential regulatory mechanisms of DGUOK-AS1 on its target genes. RESULTS: Our analysis revealed a significant upregulation of lncRNA DGUOK-AS1 in MIBC compared with NMIBC. Functionally, DGUOK-AS1 was found to enhance the proliferation and invasion of bladder cancer (BC) cells by interacting with elongation factor Tu GTP binding domain containing 2 (EFTUD2), a 116-kDa U5 small nuclear ribonucleoprotein component. Mechanistically, DGUOK-AS1 directly binds to EFTUD2 and the deubiquitinating protein valosin-containing protein-interacting protein 1, thereby shielding EFTUD2 from ubiquitination and subsequent degradation. Furthermore, EFTUD2 orchestrates the exclusion of cassette exon 11 from macrophage-stimulating 1 receptor, leading to the production of the RON∆165 isoform. This isoform activates the Akt/PKB signaling pathway, which is crucial for cancer progression. CONCLUSION: DGUOK-AS1 drives BC progression via the EFTUD2/MST1R/Akt axis, offering a promising therapeutic target for BC treatment.
Alteration of HER2 Status Following Neoadjuvant Chemotherapy in Breast Cancer: A Clinicopathological Analysis Focusing on HER2-Low Status.
Sung HJ, Kwon HJ, Bai K … +7 more , Chung YR, Shin HC, Kim EK, Suh KJ, Kim SH, Kim JH, Park SY
Cancer Res Treat · 2025 Sep · PMID 40968607 · Publisher ↗
PURPOSE: This study aimed to investigate alteration of HER2 status after neoadjuvant chemotherapy (NAC) in breast cancer and its impact on clinical outcomes of patients, focusing on HER2-low status. MATERIALS AND METHODS...
PURPOSE: This study aimed to investigate alteration of HER2 status after neoadjuvant chemotherapy (NAC) in breast cancer and its impact on clinical outcomes of patients, focusing on HER2-low status. MATERIALS AND METHODS: We retrospectively reviewed clinicopathological data of 1,063 breast cancer patients who underwent NAC between 2013 and 2020. Using paired samples of 670 patients with residual disease after NAC, we analyzed HER2 discordance rates between pre- and post-NAC samples, relationships between HER2 discordance and clinicopathological characteristics of tumors, and clinical outcomes of the patients. RESULTS: Pre-NAC HER2-low status was associated with a lower pathological complete response rate and higher Residual Cancer Burden class compared with HER2-zero and HER2-positive status. However, in subgroup analysis by hormone receptor (HR) status, no statistical differences were found in chemo-responsiveness between them. Following NAC, the overall HER2 discordance rate was 21.2% (κ = 0.676), and the most common type of alteration was zero-to-low (11.5%) conversion, followed by low-to-positive (3.6%) conversion. HER2 discordance was significantly associated with lower HER2 levels and HR positivity before NAC, as well as lymphovascular invasion, higher ypT stage, and axillary node metastasis in residual disease after NAC. In survival analyses, HER2 discordance was found to be an independent prognostic factor for poor disease-free survival of the patients, particularly within the HR-positive subgroup. CONCLUSION: Given the prognostic implications of HER2 discordance which primarily involves zero-to-low conversion and the therapeutic benefits of newly developed antibody-drug conjugates in HER2-low breast cancers, HER2 status should be re-evaluated in surgical resection specimens following NAC.
Tumor-Type-Specific TMB Cutoffs for Improved ICI Outcome Prediction: Large-Scale Analysis with Real-World Targeted NGS Data.
Jun HR, Lee JY, Lee C … +1 more , Chun SM
Cancer Res Treat · 2025 Sep · PMID 40968606 · Publisher ↗
PURPOSE: Tumor mutational burden (TMB) is a potential biomarker for predicting response to immune checkpoint inhibitors (ICIs). However, its clinical utility is limited by methodological inconsistencies. This study aimed...
PURPOSE: Tumor mutational burden (TMB) is a potential biomarker for predicting response to immune checkpoint inhibitors (ICIs). However, its clinical utility is limited by methodological inconsistencies. This study aimed to evaluate the predictive value of TMB for ICI outcomes using next-generation sequencing (NGS) data. MATERIALS AND METHODS: We retrospectively analyzed 9,459 patients with cancer who underwent tumor-only targeted NGS. TMB-high (TMB-H) cutoffs were defined using an interquartile range (IQR)-based method and validated by comparing the overall survival (OS) and progression-free survival (PFS) in ICI-treated cohorts against both The Cancer Genome Atlas whole-exome sequencing-derived TMB and the universal 10 mutations per megabase (mut/Mb) cutoff. We also examined programmed cell death-ligand 1 (PD-L1) expression and subclonality to address response heterogeneity. RESULTS: IQR-based TMB-H was significantly associated with longer PFS in the ICI-treated cohort (hazard ratio (HR)=0.85, 95% confidence interval (CI): 0.73-0.98, p=0.02), NGS before ICI subgroup (HR=0.86, p=0.049), and pre-ICI subgroup (HR=0.80, p=0.03). In contrast, the universal 10 mut/Mb cutoff showed no statistical significance. Subgroup analysis revealed significant PFS benefit in bladder (p=0.014), bowel (p=0.013), and uterine cancers (p=0.006). In lung cancer, patients with both TMB-H and very high PD-L1 expression (≥90%) had the longest PFS (HR=0.64, 95% CI: 0.44-0.93, p=0.021). Among the TMB-H samples, high subclonality was associated with worse OS in non-hypermutated cases (p=0.032). CONCLUSION: Real-world TMB cutoffs derived from distribution-based methods offer improved predictive value for ICI outcomes. Integration of the PD-L1 expression and subclonality status further refines the predictive utility of TMB, improving precision in ICI treatment.
Noninvasive Assessment of Ki-67 Expression in Breast Cancer Using Ultrasound Radiomics: A Multi-Institutional Study.
Mo S, Huang Z, Zheng J … +7 more , Wu H, Tang S, Wang M, Xu J, Tian H, Huang X, Dong F
Cancer Res Treat · 2025 Sep · PMID 40935680 · Publisher ↗
PURPOSE: This study aimed to develop and rigorously evaluate machine learning models using ultrasound (US) breast cancer (BC) images to predict Ki-67 expression. Additionally, the study sought to identify independent fac...
PURPOSE: This study aimed to develop and rigorously evaluate machine learning models using ultrasound (US) breast cancer (BC) images to predict Ki-67 expression. Additionally, the study sought to identify independent factors influencing Ki-67 expression, with further test conducted through external datasets. MATERIALS AND METHODS: This study analyzed US images of BC from 347 patients (training set: n = 230; external test set: n=117) from Shenzhen People's Hospital and Guangxi Academy of Medical Sciences. Radiomic features were extracted using manual region-of-interest (ROI) delineation and the Pyradiomics package. Feature selection was performed using LASSO and decision tree analysis, resulting in 16 features. Machine learning models-logistic regression (LR), support vector machine (SVM), and multilayer perceptron (MLP)-were developed, and their performance was assessed using the area under the receiver operating characteristic curve (ROC), accuracy, sensitivity, specificity, and decision curve analysis. Statistical analysis included univariate and multivariate logistic regression. RESULTS: Three machine learning models (LR, SVM, MLP) were developed to predict Ki-67 expression from US images. The LR model demonstrated the best diagnostic performance, with an AUC of 0.800 in external test set. Key predictors of Ki-67 expression included ill-defined mass maximum Maximum diameter and HER2 expression, along with other significant clinical variables. CONCLUSION: This dual-center study demonstrates the potential of radiomics models based on US BC images to predict Ki-67 expression accurately. As a non-invasive diagnostic tool, this approach offers valuable support for clinical decision-making and personalized treatment planning in BC patients.
Synergistic Anticancer Effects of Lenvatinib and Celastrol via ROS-Mediated ER Stress and JNK Signaling in Colon Cancer Cells.
Yan Y, Qiu C, Fu W … +9 more , Shu C, Xu C, Chen Y, Xia Y, Chen J, Chen Y, Cui R, Zou P, Ni D
Cancer Res Treat · 2025 Sep · PMID 40935679 · Publisher ↗
PURPOSE: Colon cancer, a predominant contributor to global cancer mortality, is characterized by uncontrolled cell growth in the colon or rectum. Therapeutic progress notwithstanding, including targeted therapies and che...
PURPOSE: Colon cancer, a predominant contributor to global cancer mortality, is characterized by uncontrolled cell growth in the colon or rectum. Therapeutic progress notwithstanding, including targeted therapies and chemotherapy, the survival rate remains unsatisfactory, especially for patients with advanced colon cancer, underscoring the need for novel strategies to enhance treatment efficacy. MATERIALS AND METHODS: In this study, we employed Western blot analysis to quantify target protein expression levels and immunofluorescence for protein detection and localization. To evaluate drug interactions, we calculated the Combination Index (CI). Intracellular ROS levels were measured using the DCFH-DA probe. Additionally, we generated target gene-knockdown cell lines via recombinant lentivirus transfection. For in vivo validation, we established a xenograft tumor model in nude mice to assess the therapeutic efficacy of the drug combination. RESULTS: In the study, we systematically evaluated the combinatorial potential of clinically approved lenvatinib and bioactive celastrol against colorectal cancer pathogenesis. Our results demonstrated that the combination treatment significantly inhibited cancer cell proliferation by enhancing reactive oxygen species (ROS) generation. This oxidative stress activated the ATF4-CHOP and JNK signaling pathways, ultimately inducing cell apoptosis as the main cause of death phenomenon. CONCLUSION: Our research demonstrates that celastrol potentiates lenvatinib's anti-tumor effects in colon cancer by inducing ROS-dependent ER stress and triggering phosphorylation-dependent JNK pathway activation. These findings revealing a promising combinatorial strategy to enhance therapeutic efficacy in colorectal carcinoma.
Analysis of T Cell Subsets Using Multiplex Immunohistochemistry and Clinical Outcomes of Immune Checkpoint Inhibitors in Advanced Gastric Cancer Patients.
Kim TY, Yoon J, Lee DW … +3 more , Kwak Y, Lee HS, Oh DY
Cancer Res Treat · 2025 Sep · PMID 40935678 · Publisher ↗
PURPOSE: As immunotherapy has become essential in the treatment of gastric cancer (GC), there has been growing interest in T-cells, which play a key role in immunotherapy. In this study, we evaluated the impact of T-cell...
PURPOSE: As immunotherapy has become essential in the treatment of gastric cancer (GC), there has been growing interest in T-cells, which play a key role in immunotherapy. In this study, we evaluated the impact of T-cell subsets on immune responsiveness to immune checkpoint inhibitors (ICIs) in GC using multiplex immunohistochemistry (mIHC). MATERIALS AND METHODS: Eighty-four GC patients treated with ICIs were enrolled, and we repeated the staining-scanning-stripping procedure nine times to assess different kinds of T-cells or cell-surface immune checkpoints in a single tissue section. RESULTS: The proportions of patients with microsatellite instability-high (MSI-H), Epstein-Barr virus (EBV), and non-MSI/non-EBV were 8.3%, 3.6% and 88.1%. A high cytotoxic T-cell (Tcyto) density was related to longer overall survival (OS). GC with a high ratio of Tcyto/total T-cells (Ttotal) and a low ratio of regulatory T-cells (Treg)/Ttotal showed better OS. A high density of PD-1- or TIM-3- expressing Tcyto were also associated with longer OS than a low density of those. Among memory T-cells (Tmem) subsets, GC with a high ratio of memory Tcyto/Tmem and a low ratio of memory Treg/Tmem showed prolonged OS. Better tumor responses were observed in GC with a high ratio of Tcyto/Ttotal and memory Tcyto/Tmem. CONCLUSION: T-cell subsets within the tumor microenvironment were associated with the clinical efficacy of ICIs in GC. PD-1- or TIM-3 expressing T-cells were also associated with response to ICIs, while memory T-cells subsets were associated with survival. mIHC is a feasible method for evaluating T-cell subsets in archival gastric tumor tissue.
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