Cancer Science最新文献_第2页

cGAS–STING Pathway Activation Enhances Antitumor Effect of Talaporfin Photodynamic Therapy Through ROS Production cGAS-STING通路激活通过ROS生成增强塔拉波芬光动力治疗的抗肿瘤作用。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-07-27 DOI: 10.1111/cas.70162

Makiko Sasaki, Mamoru Tanaka, Yasunari Sasaki, Yuki Kojima, Taketo Suzuki, Hirotada Nishie, Shigeki Fukusada, Naomi Sugimura, Keiji Ozeki, Takaya Shimura, Eiji Kubota, Hiromi Kataoka

{"title":"cGAS–STING Pathway Activation Enhances Antitumor Effect of Talaporfin Photodynamic Therapy Through ROS Production","authors":"Makiko Sasaki, Mamoru Tanaka, Yasunari Sasaki, Yuki Kojima, Taketo Suzuki, Hirotada Nishie, Shigeki Fukusada, Naomi Sugimura, Keiji Ozeki, Takaya Shimura, Eiji Kubota, Hiromi Kataoka","doi":"10.1111/cas.70162","DOIUrl":"10.1111/cas.70162","url":null,"abstract":"Photodynamic therapy (PDT) is a noninvasive anticancer treatment that uses a photosensitizer and light irradiation. PDT generates reactive oxygen species (ROS), thereby inducing tumor cell death. Stimulation of the interferon gene (STING) activation is highlighted as an immunotherapeutic strategy for cancer treatment. However, the role of STING and ROS in cancer therapy remains unclear. We hypothesized that STING regulates ROS generation in PDT, and that STING loss alters ROS homeostasis and causes therapeutic resistance. We established STING knockout (KO) HCT116 cells and compared the therapeutic efficacy of talaporfin sodium (TS)-PDT in KO and parental cells. Cell death induction was analyzed by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. ROS induction was analyzed using 2′,7′-dichlorofluorescin diacetate assay. STING-regulated gene activation was assessed by western blotting. Furthermore, the efficacy of STING agonist (2′-3′-cyclic GMP–AMP sodium and ADU-S100) and TS-PDT combination was assessed in a xenograft tumor model. STING KO suppressed cell death induced by TS-PDT (IC50 16.58 [±1.03] vs. 19.21 [±1.38] μmol/L). STING KO suppressed ROS generation of TS-PDT (mean fluorescence intensity, 4240 [±517.4] vs. 2234 [±551.9]). STING-dependent signaling was enhanced by TS-PDT, and these effects were eliminated by STING loss. The combination of STING agonist and TS-PDT exhibited significantly greater tumor growth inhibition than single therapy alone. STING is an important regulator of cellular ROS homeostasis and tumor cell susceptibility to ROS in PDT. Combining a STING agonist with PDT could enhance its therapeutic efficacy and may have potential for future clinical applications.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 10","pages":"2677-2687"},"PeriodicalIF":4.3,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144734524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proposal for a Germline Expert Panel to Improve Variant Reclassification in Japan 在日本建立生殖系专家小组以改进变异再分类的建议。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-07-24 DOI: 10.1111/cas.70158

Kazuki Yamazawa

引用次数: 0

Single-Cell Transcription Reveals the Fibroblast Heterogeneity and Neural Cells' Significance in Desmoid Fibromatosis 单细胞转录揭示成纤维细胞异质性和神经细胞在纤维瘤病中的意义。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-07-24 DOI: 10.1111/cas.70160

Junfeng Wang, Cheng Zhou, Peng Huang, Haodong Li, Ping Xu, Yiming Zheng, Dahui Wang, Bo Ning

{"title":"Single-Cell Transcription Reveals the Fibroblast Heterogeneity and Neural Cells' Significance in Desmoid Fibromatosis","authors":"Junfeng Wang, Cheng Zhou, Peng Huang, Haodong Li, Ping Xu, Yiming Zheng, Dahui Wang, Bo Ning","doi":"10.1111/cas.70160","DOIUrl":"10.1111/cas.70160","url":null,"abstract":"Desmoid fibromatosis (DF) is a refractory tumor with a high recurrence rate, resulting in severe organ's deformity, morbidity, and mortality. The cellular characteristics of DF remain elusive. Herein, we performed single-cell RNA sequencing (scRNA-seq) to reveal the cell landscape of DF. To uncover the exclusive characteristics of DF, we compared the transcriptional profile of DF with that of keloid fibroblast (KF) and normal fibroblast (NF) in the public data (GSE163973). When compared with KF and NF, mesenchymal fibroblasts were significantly expanded in DF. The mesenchymal fibroblasts were further divided into two subtypes according to the differentiation states, among which LAMP5+ SULF1+ fibroblasts may account for the hard property of DF by promoting tumor ossification. ADAM12 and CREB3L1 were identified as the specific marker and transcription factor for DF, respectively. Both the quiescent and proliferative COL11A1+ neural cells exerted dominant roles in the maintenance of the profibrotic microenvironment in DF through modulating extracellular matrix. This study revealed the heterogeneity of fibroblasts in DF for the first time. The novel gene markers and transcription factor identified in DF and the significance of neural cells in the tumor microenvironment may point to new directions for the targeted therapy of DF in the future.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 10","pages":"2774-2787"},"PeriodicalIF":4.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endothelial-Mesenchymal Transition in Tumor Microenvironment Promotes Neuroendocrine Differentiation of Prostate Cancer 肿瘤微环境内皮-间质转化促进前列腺癌神经内分泌分化。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-07-24 DOI: 10.1111/cas.70144

Takumi Kageyama, Manabu Kato, Shiori Miyachi, Xin Bao, Sho Sekito, Yusuke Sugino, Shinichiro Higashi, Takeshi Sasaki, Kouhei Nishikawa, Yasuhiro Murakawa, Masatoshi Watanabe, Takahiro Inoue

{"title":"Endothelial-Mesenchymal Transition in Tumor Microenvironment Promotes Neuroendocrine Differentiation of Prostate Cancer","authors":"Takumi Kageyama, Manabu Kato, Shiori Miyachi, Xin Bao, Sho Sekito, Yusuke Sugino, Shinichiro Higashi, Takeshi Sasaki, Kouhei Nishikawa, Yasuhiro Murakawa, Masatoshi Watanabe, Takahiro Inoue","doi":"10.1111/cas.70144","DOIUrl":"10.1111/cas.70144","url":null,"abstract":"Neuroendocrine prostate cancer (NEPC) is a highly aggressive and treatment-resistant subtype of castration-resistant prostate cancer (CRPC) that often emerges during progression under androgen-receptor (AR) pathway inhibition. While lineage plasticity in cancer cells has been recognized as a key mechanism of resistance, the role of the tumor microenvironment in driving this transition remains unclear. Among its cellular components, vascular endothelial cells can undergo endothelial-mesenchymal transition (EndoMT), a phenotypic shift associated with tumor progression and fibrosis. Here, we investigated whether EndoMT contributes to NEPC development. Human umbilical vein endothelial cells (HUVEC) were induced to undergo EndoMT using IL-1β and TGF-β2, and are hereafter referred to as EndoMTed HUVEC. EndoMTed HUVEC promoted neuroendocrine features and functional changes in LNCaP cells. Transcriptome analysis revealed marked upregulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) in EndoMTed HUVEC. Neutralization of GM-CSF signaling using mavrilimumab, a monoclonal antibody targeting the GM-CSF receptor alpha (CSF2RA), and siRNA-mediated CSF2RA knockdown both suppressed the neuroendocrine phenotype and STAT3 signaling of LNCaP cells. Conversely, GM-CSF stimulation alone reproduced these changes. Enzalutamide-treated LNCaP cells secreted IL-1β and TGF-β2, which in turn triggered EndoMT, suggesting a reciprocal loop. These findings indicate that anti-androgen therapy may inadvertently promote NEPC through a paracrine loop involving tumor-derived cytokines and endothelial GM-CSF secretion, highlighting EndoMT as a microenvironmental driver of treatment resistance.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 10","pages":"2712-2722"},"PeriodicalIF":4.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intrinsic PDL1 Signaling Modulates TGFBI-Mediated Growth Suppression in Lung Adenocarcinoma 内在PDL1信号调节tgfbi介导的肺腺癌生长抑制。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-07-23 DOI: 10.1111/cas.70150

Thi Thanh Nha Nguyen, Pei-Yu Chen, Ming-Yi Zheng, Ting-Kuang Lin, Chun-Chao Wang, Yuh-Min Chen, Yu-Ting Chou

{"title":"Intrinsic PDL1 Signaling Modulates TGFBI-Mediated Growth Suppression in Lung Adenocarcinoma","authors":"Thi Thanh Nha Nguyen, Pei-Yu Chen, Ming-Yi Zheng, Ting-Kuang Lin, Chun-Chao Wang, Yuh-Min Chen, Yu-Ting Chou","doi":"10.1111/cas.70150","DOIUrl":"10.1111/cas.70150","url":null,"abstract":"Programmed death ligand 1 (PDL1) suppresses T-cell immunity by engaging programmed cell death protein 1 (PD1), and its blockade can activate T-cell responses. Although PDL1 is a transmembrane protein, its intrinsic signaling role in regulating oncogenesis remains unclear. Our study reveals lung adenocarcinomas (ADCs) exhibit deficient PDL1 expression, which correlates with poor patient prognosis. TGF-β stimulation induced PDL1 expression, while silencing PDL1 in PDL1-high lung ADC cells enhanced colony formation, and PDL1 overexpression inhibited lung cancer cell growth. Cell cycle analysis indicated that PDL1 silencing increased S-phase entry in lung ADC cells. Furthermore, PDL1 expression reduced FAK, ERK, and AKT phosphorylation, increasing cell detachment from the substrate. Gene expression profiling identified TGFBI as a downstream molecule of PDL1. TGF-β induced TGFBI expression, and knockdown of TGFBI increased the growth of lung ADC cells. Given that TGF-β regulates CITED2 and p21CIP1 to initiate cell growth arrest, we examined the PDL1-TGFBI axis's impact on these molecules. Knockdown of PDL1 or TGFBI induced CITED2 expression but decreased p21CIP1 expression in lung ADC cells. Moreover, inhibiting FAK via pharmacologic or genetic approaches decreased CITED2 but increased p21CIP1 expression in PDL1-silenced lung ADC cells. These findings suggest that intrinsic PDL1-TGFBI signaling inhibits FAK activation, affecting the CITED2 molecular switch, which induces p21CIP1, ultimately leading to cell growth arrest. Our study provides insights into intrinsic PDL1 signaling in lung ADC oncogenesis and indicates that PDL1 expression could be a biomarker for lung ADC progression.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 10","pages":"2737-2749"},"PeriodicalIF":4.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Black Hole of Immune Checkpoint Blocking Therapy for Gastric Cancer: Hyperprogressive Disease 免疫检查点阻断治疗胃癌的黑洞：超进展性疾病。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-07-23 DOI: 10.1111/cas.70143

Zhuan-Fang Wang, Chen-Hui Ma, Ewetse Paul Maswikiti, Qin-Ying Han, Li-Juan He, Ben Liu, Zhi-Jian Han, Hao Chen

{"title":"The Black Hole of Immune Checkpoint Blocking Therapy for Gastric Cancer: Hyperprogressive Disease","authors":"Zhuan-Fang Wang, Chen-Hui Ma, Ewetse Paul Maswikiti, Qin-Ying Han, Li-Juan He, Ben Liu, Zhi-Jian Han, Hao Chen","doi":"10.1111/cas.70143","DOIUrl":"10.1111/cas.70143","url":null,"abstract":"In recent years, immune checkpoint inhibitors (ICIs) represented by PD-1/PD-L1 monoclonal antibodies have shown some good efficacy in various solid tumors such as gastric cancer. However, only about less than 30% of patients benefit from ICIs, and some patients experience rapid tumor growth posttreatment, known as hyperprogressive disease (HPD). Collectively, the overall survival of HPD patients is significantly shorter compared to patients with traditional disease progression, and there is no unified criterion for diagnosing HPD. Some biological mechanisms of HPD in gastric cancer caused by ICIs are still unclear, and factors associated with the occurrence of HPD are uncertain. Notably, it is believed that intrinsic factors, such as abnormal expression of oncogenic genes, and extrinsic factors, including remodeling of the tumor microenvironment, “drift” of immune cell subtypes, may be related to the occurrence of HPD in gastric cancer. Due to its immune stimulatory effects, ICIs may activate certain oncogenic pathways within the tumor, resulting in the appearance of tumor HPD phenomena through increased expression and mutations of some genes, as well as disruption of the balance between immune cells and tumor cells in the tumor microenvironment. Therefore, this review summarizes the mechanisms, predictive biomarkers, prevention, and treatment methods of HPD after immune checkpoint blockade therapy, providing a theoretical basis for making a judgment on the efficacy of ICI treatment for gastric cancer.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 10","pages":"2630-2639"},"PeriodicalIF":4.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

APE1 Attenuates ALK Tyrosine Kinase Inhibitors Sensitivity in NPM1-ALK Positive Anaplastic Large Cell Lymphoma APE1减弱NPM1-ALK阳性间变性大细胞淋巴瘤中ALK酪氨酸激酶抑制剂的敏感性。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-07-23 DOI: 10.1111/cas.70148

Zheng Liu, Xinming Jing, Dong Li, Lingbo Bao, Yi Liu, Ruyi Hang, Xunjie Kuang, Ziqi Jiang, Xiaoyan Dai, Xueling Tong, Gianluca Tell, Mengxia Li

{"title":"APE1 Attenuates ALK Tyrosine Kinase Inhibitors Sensitivity in NPM1-ALK Positive Anaplastic Large Cell Lymphoma","authors":"Zheng Liu, Xinming Jing, Dong Li, Lingbo Bao, Yi Liu, Ruyi Hang, Xunjie Kuang, Ziqi Jiang, Xiaoyan Dai, Xueling Tong, Gianluca Tell, Mengxia Li","doi":"10.1111/cas.70148","DOIUrl":"10.1111/cas.70148","url":null,"abstract":"Anaplastic lymphoma kinase (ALK), a tyrosine kinase receptor of the RTK insulin superfamily, was named after its initial identification in anaplastic large cell lymphoma (ALCL). Following a reciprocal chromosomal translocation with nucleophosmin 1 (NPM1), ALK protein is abnormally expressed, promoting the malignant transformation of T cells into a more aggressive lymphoma. The inhibition of ALK activity could therefore benefit ALK+ ALCL patients. Despite the market availability and success of ALK tyrosine kinase inhibitors (TKIs), real-world ALK+ ALCL patients exhibit significant heterogeneity in terms of disease stage at first diagnosis, tumor progression, and responses to medication. This indicates a need for more detailed differentiation of ALK+ ALCL patients in clinical practice. Here, we discovered that apurinic/apyrimidinic endonuclease-reduction/oxidation factor 1 (APE1/REF1), an interacting partner of NPM1, could stabilize NPM1-ALK fusion protein oligomers and enhance ALK tumor-promoting activity and growth, decreasing cell sensitivity to ALK-TKIs. Our results also reveal that disruption of the interaction weakens cell growth and augments the therapeutic efficacy of crizotinib and alectinib, ALK-TKIs, against ALK+ ALCL. Thus, high expression of APE1 indicates a faster growth of ALK+ ALCL; targeting this interaction may potentially achieve improved therapeutic outcomes, providing a reference for more precise treatment of ALK+ ALCL patients in clinical practice.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 10","pages":"2723-2736"},"PeriodicalIF":4.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CircCDYL Association With hnRNPL Modulates CDYL Isoform Switching in Breast Cancer Cells CircCDYL与hnRNPL的关联调节乳腺癌细胞中CDYL亚型的转换。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-07-23 DOI: 10.1111/cas.70152

Serena Bernardi, Giorgia Risso, Lorenzo Franchitti, Alessandro Camandona, Jean-Marie Robbin, Isabella Tarulli, Giulio Ferrero, Lucia Coscujuela Tarrero, Valentina Miano, Michele De Bortoli, Ymera Pignochino, Santina Cutrupi

{"title":"CircCDYL Association With hnRNPL Modulates CDYL Isoform Switching in Breast Cancer Cells","authors":"Serena Bernardi, Giorgia Risso, Lorenzo Franchitti, Alessandro Camandona, Jean-Marie Robbin, Isabella Tarulli, Giulio Ferrero, Lucia Coscujuela Tarrero, Valentina Miano, Michele De Bortoli, Ymera Pignochino, Santina Cutrupi","doi":"10.1111/cas.70152","DOIUrl":"10.1111/cas.70152","url":null,"abstract":"Circular RNAs (circRNAs) are covalently closed back-splicing products involved in the regulation of different cellular processes, and their dysregulation has been frequently observed in cancer cells. CircCDYL, a circRNA derived from the back-splicing of CDYL exon 4, has an emerging role in breast cancer (BC) biology. In this study, we investigated the role of circCDYL in modulating alternative splicing (AS) and isoform switching in MCF-7 BC cells. The circRNA profiling in MCF-7 showed circCDYL as the most abundant circRNA, with an expression increasing upon Estrogen Receptor α (ERα) silencing. RNA-Sequencing analysis of circCDYL knock-down cells revealed significant alterations in the splicing pattern, with over 2900 AS events significantly affected. Through RNA immunoprecipitation and RNA pull-down assays, we found evidence of an association between circCDYL and the splicing factor hnRNPL. To explore the consequences of this association, we compared the RNA-Sequencing of hnRNPL-silenced cells, unraveling 96 overlapping AS events accompanied by a switching usage of 223 isoforms, including those of CDYL. The self-loop regulation of circCDYL on its host gene was confirmed by isoform-specific qRT-PCR, observing that it was primarily dependent on an alternative promoter usage, rather than an AS regulation. Accordingly, epigenetic changes at CDYL alternative promoters were confirmed in circCDYL and hnRNPL knockdown cells. The confirmation of a chromatin occupancy of hnRNPL and ERα at CDYL-regulated promoters supported the role of these proteins in CDYL regulation. Our results support a synergic activity of circCDYL and hnRNPL in the regulation of AS and promoter usage in BC cells.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 10","pages":"2750-2762"},"PeriodicalIF":4.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biodegradable 3D Injectable Amino Acid Hydrogels Delivering Immune Adjuvant for Enhancing Immunotherapy in Colon Cancer 生物可降解的3D可注射氨基酸水凝胶提供免疫佐剂以增强结肠癌的免疫治疗。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-07-23 DOI: 10.1111/cas.70156

Mengfei Yin, Ling Mao, Xunlei Zhang, Jiali Ji, Li Song, Qingxia Ma, Donglin Xia, Lei Yang

{"title":"Biodegradable 3D Injectable Amino Acid Hydrogels Delivering Immune Adjuvant for Enhancing Immunotherapy in Colon Cancer","authors":"Mengfei Yin, Ling Mao, Xunlei Zhang, Jiali Ji, Li Song, Qingxia Ma, Donglin Xia, Lei Yang","doi":"10.1111/cas.70156","DOIUrl":"10.1111/cas.70156","url":null,"abstract":"Cancer immunotherapy using toll-like receptor agonists (R837) has been extensively investigated and demonstrates potential as an effective adjuvant. Due to the potential for severe side effects associated with R837, the subcutaneous injection of a hydrogel scaffold may enhance its efficacy. Herein, we propose a biodegradable 3D injectable scaffold as an injectable delivery carrier for R837 (R837@Gel), to control the release rate of R837 and be friendly to subcutaneous tissue. Biodegradable 3D injectable amino acid hydrogels were constructed by catalase effect during Fmoc-Phe and Phe2 substrates. After subcutaneous injection, R837@Gel formed a hydrogel-like component, provided adequate 3D support, and released R837 in order owing to the decomposition of amino acids. Effective CD4+ and CD8+ T-cell responses were observed, promoted by R837@Gel (p < 0.001). The amino acid hydrogel scaffold exhibited a favorable safety profile and could be degraded successfully. The biodegradable 3D injectable amino acid hydrogels prolonged the action duration of R837 and markedly enhanced the efficacy of PD-1. The 3D amino acid hydrogel scaffold encapsulating R837 in combination with immune checkpoint blockade represents a potent strategy for enhancing antitumor immunotherapy while mitigating systemic toxicity concerns. Moreover, controlled drug administration via subdermal implants has significant potential for reducing the compliance burden associated with frequent dosing. The combination of biocompatibility, ease of modification, and the ability to create a 3D microenvironment makes amino acid hydrogels a valuable tool in the field of regenerative medicine and tissue engineering.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 10","pages":"2846-2857"},"PeriodicalIF":4.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aurora-A Promotes Cell-Cycle Progression From Quiescence Through Primary Cilia Disassembly Aurora-A促进细胞周期从静止到初级纤毛的拆卸。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-07-22 DOI: 10.1111/cas.70153

Atsushi Kohso, Hironori Inaba, Masato T. Kanemaki, Esteban C. Gabazza, Hidemi Toyoda, Masahiro Hirayama, Hidemasa Goto

{"title":"Aurora-A Promotes Cell-Cycle Progression From Quiescence Through Primary Cilia Disassembly","authors":"Atsushi Kohso, Hironori Inaba, Masato T. Kanemaki, Esteban C. Gabazza, Hidemi Toyoda, Masahiro Hirayama, Hidemasa Goto","doi":"10.1111/cas.70153","DOIUrl":"10.1111/cas.70153","url":null,"abstract":"Aurora-A (AurA) is a member of the mitotic kinase family and is highly expressed in various tumors. Inhibition of AurA generally leads to fetal mitotic errors. We previously reported that AurA inhibition induces G0/G1 cell cycle arrest in noncancerous cells by promoting the reassembly of primary cilia. However, the mechanisms by which AurA regulates cell cycle progression beyond mitosis remain largely unknown. In this study, we generated noncancerous RPE1 and cancerous HCT116 cell lines expressing endogenous AurA tagged with a minimal auxin-inducible degron (mAID) using CRISPR/Cas9-based gene editing. This system enabled specific and rapid depletion of endogenous AurA protein. By combining this approach with cell synchronization in RPE1 cells, we investigated AurA function specifically in the transition from quiescence to the proliferative cell cycle. Targeted degradation of AurA not only delayed cell cycle progression but also impaired the disassembly of primary cilia at the G0/G1 transition in RPE1 cells. Since this delay in cell cycle progression was rescued by forced deciliation via the knockout of IFT20, AurA facilitates deciliation, which in turn accelerates the transition from quiescence to the proliferative phase of the cell cycle in RPE1 cells. AurA depletion for 4 days increased apoptotic markers in HCT116 cells but not in RPE1 cells. Notably, forced deciliation in RPE1 cells partially enhanced apoptosis induced by AurA depletion. These results suggest that the ability to assemble primary cilia may serve as a protective mechanism against cell death following AurA inhibition.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 10","pages":"2763-2773"},"PeriodicalIF":4.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0