Cancer Science最新文献

Targeting RNA Polymerase I in Ewing Sarcoma Treatment.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-03-12 DOI: 10.1111/cas.70047

Alexis Bruce, Gavin Anchondo, Rebekah Carter, Sergio Guerrero Pacheco, Hema Sri Kambala, Elizabeth Cortez, Kyra Parker, Le Su

引用次数: 0

LncRNA-DANCR Promotes ESCC Progression and Function as ceRNA to Regulate DDIT3 Expression by Sponging microRNA-3193.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-03-12 DOI: 10.1111/cas.70035

Heng Xiao, Tong Zhou, Yanfang Yang, Xin Yang, Yanghui Bi, Xiaolong Cheng

引用次数: 0

The Combination of PARP and Topoisomerase 1 Inhibitors Improves Radiation Therapy for Ewing Sarcoma.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-03-11 DOI: 10.1111/cas.70042

Jia Xie, Marcia M Mellado-Lagarde, Kaley Blankenship, Debolina Ganguly, Nathaniel R Twarog, Brandon Bianski, Matthew Kieffer, Stefan Atkinson, Heather Sheppard, Jessica Gartrell, Samuel Cler, Sara M Federico, Elizabeth A Stewart, Christopher L Tinkle, Anang A Shelat

{"title":"The Combination of PARP and Topoisomerase 1 Inhibitors Improves Radiation Therapy for Ewing Sarcoma.","authors":"Jia Xie, Marcia M Mellado-Lagarde, Kaley Blankenship, Debolina Ganguly, Nathaniel R Twarog, Brandon Bianski, Matthew Kieffer, Stefan Atkinson, Heather Sheppard, Jessica Gartrell, Samuel Cler, Sara M Federico, Elizabeth A Stewart, Christopher L Tinkle, Anang A Shelat","doi":"10.1111/cas.70042","DOIUrl":"https://doi.org/10.1111/cas.70042","url":null,"abstract":"Although primary tumor control rates after surgery and/or radiation therapy (RT) are generally high in patients with Ewing sarcoma (EWS), those with unresectable tumors have failure rates approaching 30% and experience poorer outcomes. Additionally, although metastatic site irradiation is associated with improved survival, dose, and volume effects influence the long-term toxicity risk. Consequently, it is important to identify novel systemic agents to enhance the therapeutic ratio of RT. Given the reported DNA damage response deficits in EWS, we hypothesized that PARP inhibitors (PARPis) would preferentially potentiate radiation relative to standard-of-care (SOC) chemotherapeutics. We investigated primary and recurrent SOC drugs and PARPis with varied trapping potential in combination with radiation in EWS cell lines. At physiologically relevant concentrations, the strong PARP trapper talazoparib (TAL) potentiated radiation to a greater extent than did SOC or other PARPis, although the magnitude of the effect was modest. The radiosensitizing effect of TAL was mediated through the induction of DNA double-strand breaks, rather than through the catalytic inhibition of PARP1. Drug + RT combinations were further tested in vivo by using orthotopic xenograft models of EWS treated with image-guided fractionated radiation. The addition of RT to the combination of TAL plus irinotecan (IRN), a recently evaluated clinical regimen for relapsed pediatric solid tumors, significantly prolonged survival and reduced tumor burden in all EWS-treated mice. This triplet therapy (TAL + IRN + RT) was feasible and yielded responses in several patients with EWS and may represent a useful salvage strategy in recurrent or progressive disease.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of Minimal Residual Disease on Early Recurrence of Liver Metastatic Colorectal Cancer.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-03-10 DOI: 10.1111/cas.16442

Mampei Kawashima, Takeshi Yamada, Toshimitsu Miyasaka, Shintaro Kanaka, Sho Kuriyama, Kay Uehara, Akihisa Matsuda, Ryo Ohta, Hiromichi Sonoda, Nobuhiko Taniai, Hiroshi Yoshida

{"title":"Impact of Minimal Residual Disease on Early Recurrence of Liver Metastatic Colorectal Cancer.","authors":"Mampei Kawashima, Takeshi Yamada, Toshimitsu Miyasaka, Shintaro Kanaka, Sho Kuriyama, Kay Uehara, Akihisa Matsuda, Ryo Ohta, Hiromichi Sonoda, Nobuhiko Taniai, Hiroshi Yoshida","doi":"10.1111/cas.16442","DOIUrl":"https://doi.org/10.1111/cas.16442","url":null,"abstract":"For patients with resectable colorectal liver metastases (CRLM), the efficacy of adjuvant chemotherapy remains a subject of debate. Several studies have concluded that postoperative circulating tumor DNA (ctDNA) is a marker of minimal residual disease (MRD) and is a useful prognostic factor in patients with nonmetastatic colorectal cancer. However, few studies have explored its application in cases involving metastases. This was an observational study that included CRLM patients who underwent primary and liver tumor resection. By examining targeted sequencing of 50 genes commonly mutated in CRC, we identified at least one somatic mutation in each patient's metastatic liver tumor. Blood samples were obtained before and 1-month after surgery. Fifty-three patients were included, and recurrence was diagnosed in 39 patients. Of those, 13 patients experienced early relapse. ctDNA was detected in 45 patients before surgery and 11 after. All MRD-positive patients experienced recurrence. Among them, nine had early recurrence. MRD-positive patients had poorer recurrence free survival (RFS, p < 0.0001) and overall survival (OS, p < 0.0005). Nine of 13 patients with early recurrence had MRD; however, two of 40 patients without early recurrence also had MRD (p < 0.0001). Among 42 MRD-negative patients, adjuvant chemotherapy had no impact of RFS (p = 0.84) or OS (p = 0.54). MRD proved valuable in predicting the risk of postoperative recurrence in patients with CRLM, particularly because MRD positivity emerged as a significant risk factor for early recurrence. Furthermore, it appears that adjuvant chemotherapy may not effectively improve the prognosis for MRD-negative patients.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Risk Stratification Prediction of Endometrial Cancer Using Microstructural Mapping Based on Time-Dependent Diffusion MRI.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-03-10 DOI: 10.1111/cas.70036

Yu Zhao, Feng Zhao, Meng Cheng, Gang Wang, Dan Wang, Huijuan Yin, Zhixiao Xue, Yule Chen, Zhen Zhao, Hui Ma, Xiaoxiao Zhang, Junping Wang, Fengtan Li

{"title":"Risk Stratification Prediction of Endometrial Cancer Using Microstructural Mapping Based on Time-Dependent Diffusion MRI.","authors":"Yu Zhao, Feng Zhao, Meng Cheng, Gang Wang, Dan Wang, Huijuan Yin, Zhixiao Xue, Yule Chen, Zhen Zhao, Hui Ma, Xiaoxiao Zhang, Junping Wang, Fengtan Li","doi":"10.1111/cas.70036","DOIUrl":"https://doi.org/10.1111/cas.70036","url":null,"abstract":"Time-dependent diffusion MRI (td-dMRI) has potential in characterizing microstructural features; however, its value in imaging endometrioid endometrial adenocarcinoma (EEA) remains uncertain. Patients surgically confirmed with EEA were finally enrolled in our study. The td-dMRI data were acquired using pulsed gradient spin echo sequence and oscillating gradient spin echo sequences. The microstructural markers, including cell diameter, intracellular volume fraction (Vin), cellularity, and extracellular diffusivity (Dex), were fitted with the imaging microstructural parameters using a limited spectrally edited diffusion (IMPULSED) model. The parameters were compared between low- and high-risk groups and between low- and high-proliferation groups. The diagnostic performance was evaluated using receiver-operating characteristic curve and logistic regression analysis. Diameter, Dex, ADCPGSE, ADCN1, and ADCN2 were significantly low, whereas cellularity, ΔADC1 and ΔADC2 were significantly high in the high-risk and high-proliferation groups. Cellularity, ΔADC1, and ΔADC2 demonstrated excellent diagnostic efficacy in predicting both risk stratification and proliferation status. Cellularity was the only independent predictor for risk stratification, which exhibited a satisfactory positive correlation with cell density in histopathologic examination. The diagnostic potential of td-dMRI-based microstructural mapping was demonstrated to noninvasively probe the pathologic characteristics of patients with EEA in a clinical setting, which provided a valuable contribution to surgical guidance.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FN1 Immunoregulation in Glioblastoma: Insights From Neutrophil-Centric Studies.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-03-07 DOI: 10.1111/cas.70041

Xiangtian Meng, Xusen Yang, Junle Zhu, Huairui Chen, Chun Luo, Fenglin Zhang, Qin Zhang, Jingliang Ye

{"title":"FN1 Immunoregulation in Glioblastoma: Insights From Neutrophil-Centric Studies.","authors":"Xiangtian Meng, Xusen Yang, Junle Zhu, Huairui Chen, Chun Luo, Fenglin Zhang, Qin Zhang, Jingliang Ye","doi":"10.1111/cas.70041","DOIUrl":"https://doi.org/10.1111/cas.70041","url":null,"abstract":"Neutrophils, as key components of the tumor microenvironment, play a crucial role in cancer progression and prognosis. This study aimed to identify a neutrophil-related gene signature to improve prognostic predictions and explore potential immunotherapy targets for glioblastoma multiforme (GBM) patients. Through co-expression analysis, 60 neutrophil-associated genes were identified, showing significant enrichment in 159 Gene Ontology terms and eight KEGG pathways. Among these, 10 genes were significantly associated with patient survival, leading to the development of a six-gene risk model termed the Neutrophil-Related Gene Prognostic Index (NRGPI). The NRGPI predicted overall survival (OS) in both training and validation cohorts (p < 0.05), with enhanced prognostic accuracy when combined with clinicopathological factors. Higher NRGPI scores were correlated with worse OS, increased mortality, and more aggressive disease progression. Immune profiling linked NRGPI to immune cell infiltration, immune checkpoint expression, and tumor mutation burden, suggesting its potential in identifying candidates for immunotherapy. Among the identified genes, FN1 emerged as a central regulator, associated with immune cell composition and poor prognosis. Pan-cancer analysis revealed consistent upregulation of FN1 across cancer types, underscoring its broad clinical relevance. Additionally, tissue microarray analysis using multiplex immunofluorescence on 84 GBM samples confirmed co-expression of FN1, SDC1, and TWIST1, with higher levels associated with reduced survival. These findings establish NRGPI as a valuable prognostic biomarker for GBM, offering novel insights into the immune landscape and positioning FN1 as a promising therapeutic target for further investigation in GBM treatment.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ATR Inhibition Synergizes With Alkylating PI Polyamide Targeting MYCN by Suppressing DNA Repair in MYCN-Amplified Neuroblastoma. 通过抑制 MYCN 扩增神经母细胞瘤的 DNA 修复，ATR 抑制与针对 MYCN 的烷基化 PI 多酰胺协同作用。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-03-07 DOI: 10.1111/cas.70043

Xiaoyi Lai, Hiroyuki Yoda, Yuming Qiao, Yuki Kida, Keizo Takenaga, Yoshinao Shinozaki, Nobuko Koshikawa, Atsushi Takatori

{"title":"ATR Inhibition Synergizes With Alkylating PI Polyamide Targeting MYCN by Suppressing DNA Repair in MYCN-Amplified Neuroblastoma.","authors":"Xiaoyi Lai, Hiroyuki Yoda, Yuming Qiao, Yuki Kida, Keizo Takenaga, Yoshinao Shinozaki, Nobuko Koshikawa, Atsushi Takatori","doi":"10.1111/cas.70043","DOIUrl":"https://doi.org/10.1111/cas.70043","url":null,"abstract":"Amplification of MYCN is a major oncogenic driver of high-risk neuroblastomas. We previously developed CCC-002, a MYCN-selective pyrrole-imidazole polyamide conjugated to a DNA alkylating agent. Administration of CCC-002 to MYCN-amplified (MYCN-amp) neuroblastoma cells triggered the activation of DNA damage responses. Here, we demonstrated that among the DNA damage response inhibitors, ataxia telangiectasia and Rad3-related (ATR) inhibitors synergized with CCC-002 to suppress DNA repair-related genes and induce apoptosis in MYCN-amp neuroblastoma cells. A synergistic antitumor effect was verified in an SK-N-BE(2) xenograft mouse model, in which the combined use of CCC-002 and ATR inhibitor at low doses significantly inhibited tumor progression. Notably, SK-N-BE(2) and SK-N-DZ cells, which showed ATM activation after CCC-002 treatment, exhibited high sensitivity to the combined treatment of ATR inhibitors. Comprehensive analysis of the gene expression profiles revealed that the combination treatment upregulated apoptosis-related pathways and downregulated DNA repair-related pathways. After the combined treatment of CCC-002 and ATR inhibitor, MYCN-amp cells showed less FISH probe signal and mRNA expression of MYCN, which was accompanied by an increase in DNA damage markers in the genomic region of MYCN, highlighting that ATR inhibitors synergize with CCC-002 and play a crucial role in the development of a novel MYCN-targeting therapy for MYCN-amp neuroblastoma.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GGCT Inhibits Ferroptosis in PTC Cells by Upregulating p53 Through RPS15A.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-03-05 DOI: 10.1111/cas.70039

Hui-Min Zhang, Han-Ning Li, Enbo Qi, Yang Yang, Huiping Ma, Jie Ma, Xiwen Xiong, Jun Wang, Zhi-Fang Yang, Xing-Hua Liao

{"title":"GGCT Inhibits Ferroptosis in PTC Cells by Upregulating p53 Through RPS15A.","authors":"Hui-Min Zhang, Han-Ning Li, Enbo Qi, Yang Yang, Huiping Ma, Jie Ma, Xiwen Xiong, Jun Wang, Zhi-Fang Yang, Xing-Hua Liao","doi":"10.1111/cas.70039","DOIUrl":"https://doi.org/10.1111/cas.70039","url":null,"abstract":"γ-Glutamine cyclotransferase (GGCT) is an enzyme involved in the metabolic cycle of glutathione (GSH). Abnormal GSH metabolism is mostly related to ferroptosis. However, the mechanisms supporting aberrant GGCT expression in PTC remain to be investigated. In this study, we found that GGCT knockdown inhibited GSH synthesis and promoted malondialdehyde (MDA) and reactive oxygen species (ROS) accumulation, thereby promoting ferroptosis in papillary thyroid cancer cells. Pro-GA, the specific inhibitor of GGCT, inhibited the subcutaneous tumor formation of K1 cells. IP combined with LC-MS/MS showed an interaction between GGCT and RPS15A. RPS15A is highly expressed in PTC tissues and cells, and GGCT promotes the stability of RPS15A. Knockdown of RPS15A promoted p53 expression, which in turn inhibited SLC7A11 expression, resulting in ferroptosis, while overexpression of RPS15A reversed GGCT-induced ferroptosis. In addition, miR-205-5p targeted the 3' UTR of GGCT to inhibit GGCT-mediated ferroptosis, tumor growth, and lung metastasis. In conclusion, we found that knockdown of GGCT promoted ferroptosis in PTC cells. Mechanistically, GGCT interacts with RPS15A, and GGCT promotes the protein stability of RPS15A. Knockdown of RPS15A promotes p53 expression and inhibits SLC7A11 expression, thereby inhibiting GSH synthesis. The upstream mechanism of GGCT regulation showed that miR-205-5p inhibited GGCT protein expression by targeting the 3' UTR of GGCT.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Time Lag Associated With the Reclassification of Germline BRCA Variants' Pathogenicity Is Critical for Cancer Patients.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-03-04 DOI: 10.1111/cas.70040

Tomomi Hayashi, Hiroyuki Matsubayashi, Yoshimi Kiyozumi

引用次数: 0

Novel Approach to Overcome Osimertinib Resistance Using Bromodomain and Extra-Terminal Domain Inhibitors.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-03-04 DOI: 10.1111/cas.70032

Yosuke Miyashita, Ken Tajima, Kenta Izumi, Naohisa Matsumoto, Daisuke Hayakawa, Ikuko Takeda Nakamura, Isana Katayama, Adityo Wibowo, Hironari Matsuda, Wira Winardi, Bagus Radityo Amien, Yoichiro Mitsuishi, Fumiyuki Takahashi, Kohta Nakamura, Ken Uchibori, Noriko Yanagitani, Takuo Hayashi, Kazuya Takamochi, Kenji Suzuki, Ryohei Katayama, Kazuhisa Takahashi

{"title":"Novel Approach to Overcome Osimertinib Resistance Using Bromodomain and Extra-Terminal Domain Inhibitors.","authors":"Yosuke Miyashita, Ken Tajima, Kenta Izumi, Naohisa Matsumoto, Daisuke Hayakawa, Ikuko Takeda Nakamura, Isana Katayama, Adityo Wibowo, Hironari Matsuda, Wira Winardi, Bagus Radityo Amien, Yoichiro Mitsuishi, Fumiyuki Takahashi, Kohta Nakamura, Ken Uchibori, Noriko Yanagitani, Takuo Hayashi, Kazuya Takamochi, Kenji Suzuki, Ryohei Katayama, Kazuhisa Takahashi","doi":"10.1111/cas.70032","DOIUrl":"https://doi.org/10.1111/cas.70032","url":null,"abstract":"Osimertinib, a third-generation EGFR-tyrosine kinase inhibitor, is the first-line therapy for lung cancer harboring EGFR mutations. The mechanisms underlying osimertinib resistance are diverse, with approximately half remaining unknown. Epigenetic dysregulation is implicated in drug resistance; however, the mechanisms remain unclear. Therefore, we investigated epigenetic involvement in osimertinib resistance and its therapeutic potential. We established osimertinib-resistant cells and used an assay for transposase-accessible chromatin using sequencing to evaluate chromatin accessibility, finding significant changes post-resistance. Combining the assay for transposase-accessible chromatin and RNA sequencing data, we identified FGF1 as a resistance-related gene regulated by histone modifications. FGF1 induced osimertinib resistance, and its suppression attenuated resistance. Bromodomain and extra-terminal domain inhibitors combined with osimertinib overcame osimertinib resistance by reducing FGF1 expression. Increased FGF1 expression was observed in osimertinib-resistant clinical samples. This combination therapy was effective in cell lines and mouse xenograft models. These results suggest targeting histone modifications using bromodomain and extra-terminal domain inhibitors as a novel approach to overcoming osimertinib resistance.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0