Molecular Oncology最新文献_第5页

PARP inhibitors elicit distinct transcriptional programs in homologous recombination competent castration-resistant prostate cancer. PARP抑制剂在同源重组能性去势抵抗性前列腺癌中引发不同的转录程序。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-09-07 DOI: 10.1002/1878-0261.70098

Moriah L Cunningham, Jasibel Vasquez-Gonzalez, Samantha M Barnada, Salome Tchotorlishvili, Latese Jones, Ryan Maguire, Genevieve Lewis, Kinza Rizwan, Jenny Deng, Salma Koachar, Drithi Patel, Hailey Shankle, Tessa Mulders, Namra Ajmal, Charalambos Solomides, Emad S Alnemri, Teresa F Alnemri, Ayesha A Shafi, Leonard G Gomella, Wm Kevin Kelly, Steven B McMahon, Matthew J Schiewer

{"title":"PARP inhibitors elicit distinct transcriptional programs in homologous recombination competent castration-resistant prostate cancer.","authors":"Moriah L Cunningham, Jasibel Vasquez-Gonzalez, Samantha M Barnada, Salome Tchotorlishvili, Latese Jones, Ryan Maguire, Genevieve Lewis, Kinza Rizwan, Jenny Deng, Salma Koachar, Drithi Patel, Hailey Shankle, Tessa Mulders, Namra Ajmal, Charalambos Solomides, Emad S Alnemri, Teresa F Alnemri, Ayesha A Shafi, Leonard G Gomella, Wm Kevin Kelly, Steven B McMahon, Matthew J Schiewer","doi":"10.1002/1878-0261.70098","DOIUrl":"https://doi.org/10.1002/1878-0261.70098","url":null,"abstract":"Prostate cancer (PCa) is the second most lethal cancer in men in the US. African American (AA) men have twice the incidence and death rate of European American (EA) men. Advanced PCa shows increased expression and activity of the DNA damage/repair pathway enzyme, poly (ADP-ribose) polymerase 1 (PARP1). PARP1 inhibitors (PARPi) are FDA-approved for advanced PCa tumors with mutations in the homologous recombination repair (HRR) pathway. However, PARPi can provide benefit in model systems without HRR deficiencies. PARPi have distinct biochemical mechanisms, potencies, and toxicity profiles. While there is emerging evidence of differences in DNA damage/repair pathway enzyme expression between EA and AA men, PARP1 expression has not been fully explored in the context of race. This study hypothesized: (a) AA and EA PCa may respond differently to PARPi and (b) different PARPi may uniquely impact the transcriptome, irrespective of HRR status. Study results indicate a link between racial background and PARP1 expression/activity and define unique and overlapping transcriptional responses downstream of all five PARPi. These findings may lead to refined personalized recommendations for use of specific PARPi.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015869","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

Emerging role of ARHGAP29 in melanoma cell phenotype switching. ARHGAP29在黑色素瘤细胞表型转换中的新作用。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-09-04 DOI: 10.1002/1878-0261.70114

Beatrice Charlotte Tröster, Melanie Kappelmann-Fenzl, Anja Katrin Bosserhoff, Nicole Rachinger

{"title":"Emerging role of ARHGAP29 in melanoma cell phenotype switching.","authors":"Beatrice Charlotte Tröster, Melanie Kappelmann-Fenzl, Anja Katrin Bosserhoff, Nicole Rachinger","doi":"10.1002/1878-0261.70114","DOIUrl":"https://doi.org/10.1002/1878-0261.70114","url":null,"abstract":"Rho GTPase-activating protein 29 (ARHGAP29) is an inhibitor of the Ras homolog family member A (RhoA)/Rho-associated protein kinase (ROCK) signaling pathway. Studies in non-melanoma cancer entities described that ARHGAP29 modulates the actin cytoskeleton, promoting tumor cell invasion. In melanoma, its function has been completely unknown. Our transcriptomic analyses revealed a strong expression of ARHGAP29 in melanoma cell lines compared to melanocytes. Therefore, we hypothesized that ARHGAP29 affects the migratory potential of melanoma cells and drives melanoma progression. By knocking down ARHGAP29, we demonstrated that it promotes a spread cell morphology through regulating the RhoA/ROCK pathway. Further investigations indicated the role of ARHGAP29 on SMAD activity. Interestingly, our data showed that ARHGAP29 expression is promoting tumor cell plasticity through a mesenchymal-like, invasive phenotype. To summarize, this study gives insights into the functional role of ARHGAP29 and its downstream signaling in melanoma. Our findings provided evidence supporting the hypothesis that ARHGAP29 is an important player in melanoma progression, a promising and novel target in melanoma treatment.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000976","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

Multi-omic profiling of squamous cell lung cancer identifies metabolites and related genes associated with squamous cell carcinoma. 鳞状细胞肺癌的多组学分析鉴定了与鳞状细胞癌相关的代谢物和相关基因。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-09-03 DOI: 10.1002/1878-0261.70121

Johan Staaf, Daniel Ehinger, Hans Brunnström, Mats Jönsson, Frida Rosengren, Marija Kotevska, Anna Karlsson, Mattias Aine, Christian Frezza, Maria Planck, Elsa Arbajian

{"title":"Multi-omic profiling of squamous cell lung cancer identifies metabolites and related genes associated with squamous cell carcinoma.","authors":"Johan Staaf, Daniel Ehinger, Hans Brunnström, Mats Jönsson, Frida Rosengren, Marija Kotevska, Anna Karlsson, Mattias Aine, Christian Frezza, Maria Planck, Elsa Arbajian","doi":"10.1002/1878-0261.70121","DOIUrl":"https://doi.org/10.1002/1878-0261.70121","url":null,"abstract":"Squamous cell lung carcinoma (SqCC) is the second most common histological subtype of lung cancer. Besides tumor-initiating and promoting DNA, RNA, and epigenetic alterations, aberrant cell metabolism is a hallmark of carcinogenesis. This study aimed to identify SqCC-specific key regulators that could eventually be used as new anticancer targets. Transcriptional and metabolomic data were gathered for a cohort of resected lung cancers. SqCC-specific differentially expressed genes were integrated with metabolic data. Findings were validated in cohorts of tumors, normal specimens, and cell lines. In situ protein expression of SLC6A8 was investigated. Differential gene expression analysis identified a subset of SqCC-specific genes with metabolic functions through the Reactome database, and/or correlated to specific metabolites through GEMs models. Metabolic profiling identified seven SqCC-specific metabolites, of which increased creatine levels, in particular, matched to SqCC-specific expression of SLC6A8. Expression of the gene appeared tumor cell-associated. Elevated creatine levels and overexpression of its transporter SLC6A8 appear a distinct metabolic feature of SqCC. Considering ongoing clinical trials in other malignancies, exploring SLC6A8 inhibition in SqCC appears motivated based on a metabolic addiction hypothesis.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993011","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

MET and NF2 alterations confer primary and early resistance to first-line alectinib treatment in ALK-positive non-small-cell lung cancer. MET和NF2的改变导致alk阳性非小细胞肺癌患者对阿勒替尼一线治疗的原发性和早期耐药。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-09-01 Epub Date: 2025-04-01 DOI: 10.1002/1878-0261.70029

Jie Hu, Ning Ding, Xiaobo Xu, Yedan Chen, Yong Zhang, Jingwen Liu, Jiebai Zhou, Hairong Bao, Donghui Zhang, Yijun Song, Yang Shao, Yuanlin Song

{"title":"MET and NF2 alterations confer primary and early resistance to first-line alectinib treatment in ALK-positive non-small-cell lung cancer.","authors":"Jie Hu, Ning Ding, Xiaobo Xu, Yedan Chen, Yong Zhang, Jingwen Liu, Jiebai Zhou, Hairong Bao, Donghui Zhang, Yijun Song, Yang Shao, Yuanlin Song","doi":"10.1002/1878-0261.70029","DOIUrl":"10.1002/1878-0261.70029","url":null,"abstract":"Although first-line alectinib has prolonged survival in ALK-mutated non-small-cell lung cancers (NSCLCs), the response to treatment varies among patients, and the primary/early development of alectinib resistance mechanisms is still not fully understood. Here, we analyzed molecular profiles of 108 alectinib-treated patients (first-line and second-line after crizotinib) with confirmed relapse by targeted sequencing of cancer-related genes. After first-line treatment, off-target MET and NF2 alterations were more frequent than on-target alterations within the first 6 months, causing primary or early resistance. Conversely, on-target alterations became prevalent after 1 year of first-line alectinib treatment and predominantly after second-line. The incidence of acquired resistance also depended on EML4-ALK variants. In variant 1 (v1), off-target alterations were responsible for 50% of resistance cases after first-line alectinib therapy, whereas on-target mutations had no contribution in this subgroup. In variant 3 (v3), on-target alterations resulted in 46% of resistance cases, whereas only 18% were caused by off-target mutations. After second-line treatment, the most common mutations in v1 were L1196M (42%) and G1269A (25%), while G1202R was detected in 45% of v3 tumors. These findings emphasize the importance of stratifying resistance mechanisms to guide tailored treatment for ALK-positive NSCLCs.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2715-2729"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753406","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

Evaluation and modification of tumor cell isolation techniques from malignant effusions for rapid drug sensitivity testing. 用于快速药敏试验的恶性积液肿瘤细胞分离技术的评价与改进。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-09-01 Epub Date: 2025-06-17 DOI: 10.1002/1878-0261.70072

Navit Mooshayef, Hana Barhom, Sumit Chatterji, Netta Hecht, Oran Warhaftig, Iris Kamer, Oranit Zadok, Jair Bar, Limor Broday, Amir Onn, Michael Peled

{"title":"Evaluation and modification of tumor cell isolation techniques from malignant effusions for rapid drug sensitivity testing.","authors":"Navit Mooshayef, Hana Barhom, Sumit Chatterji, Netta Hecht, Oran Warhaftig, Iris Kamer, Oranit Zadok, Jair Bar, Limor Broday, Amir Onn, Michael Peled","doi":"10.1002/1878-0261.70072","DOIUrl":"10.1002/1878-0261.70072","url":null,"abstract":"Non-small cell lung cancer treatment decisions rely on several diagnostic steps. Tests that rely on DNA sequencing often fail to capture the full mutational landscape of tumor cells, and drug sensitivity testing (DST) has limitations hindering widespread use currently. One of the major challenges for DST is the rapid isolation of a sufficient number of live tumor cells that would allow testing of multiple drugs simultaneously. To address this challenge, we have developed a DST procedure specifically tailored for tumor cells originating from malignant pleural effusions. We first identified tumor cells by anti-epithelial cell adhesion molecule (EpCAM) flow cytometry and then compared several methods for tumor cell isolation: immunomagnetic enrichment of epithelial cells using EpCAM, negative selection via immunomagnetic CD45+ cell depletion, and size-based separation and capture of tumor cells utilizing cell strainers. Of these methods, repeated rounds of CD45+ cell depletion, in which the number of rounds is set by the initial percentage of tumor cells in the sample, were the most effective. By combining tumor cell enrichment with DST, we have developed a system which generates DST results that correlate with clinical outcomes.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2474-2490"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310214","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

A single gene mutation predicts response to immune checkpoint blockade in ovarian clear cell carcinoma. 单基因突变预测卵巢透明细胞癌对免疫检查点阻断的反应。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-09-01 Epub Date: 2025-07-30 DOI: 10.1002/1878-0261.70104

Matheus Henrique Dias, René Bernards

引用次数: 0

PoDCall: a robust tool for automated droplet classification in DNA-methylation droplet digital PCR. PoDCall：在dna甲基化液滴数字PCR中自动液滴分类的强大工具。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-09-01 Epub Date: 2025-08-05 DOI: 10.1002/1878-0261.70105

Hans Petter Brodal, Heidi Pharo, Hege Marie Vedeld, Guro E Lind

引用次数: 0

Microglia limit brain tumor development by restricting tumor cell proliferation and inducing T-cell immunity. 小胶质细胞通过抑制肿瘤细胞增殖和诱导t细胞免疫来限制脑肿瘤的发展。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-09-01 Epub Date: 2025-08-01 DOI: 10.1002/1878-0261.70102

Tzu-Chieh Sun, Ching-Fang Yu, Sheng-Yan Wu, Wei-Chung Cheng, Chi-Shiun Chiang, Fang-Hsin Chen

{"title":"Microglia limit brain tumor development by restricting tumor cell proliferation and inducing T-cell immunity.","authors":"Tzu-Chieh Sun, Ching-Fang Yu, Sheng-Yan Wu, Wei-Chung Cheng, Chi-Shiun Chiang, Fang-Hsin Chen","doi":"10.1002/1878-0261.70102","DOIUrl":"10.1002/1878-0261.70102","url":null,"abstract":"Tumor-associated macrophages (TAMs) in brain tumors contain two types of macrophages: tumor-associated microglia and infiltrating macrophages. This study explored whether these two populations have the same role in brain tumor progression. In an in vitro coculture model using the astrocytoma cells ALTS1C1 with either the microglial cell line BV2 or the peripheral macrophage cell line RAW264.7, only BV2, not RAW264.7, gathers ALTS1C1 into tumor cell clusters. These BV2-associated clusters limited ALTS1C1 proliferation but not BV2 cell growth. The in vivo studies show that the survival time of mice co-inoculated with ALTS1C1 and BV2 was prolonged from 30.4 ± 3.1 days to more than 77 days in immune-competent mice but not in immune-compromised mice. Examining the tumor microenvironment (TME) by immunohistochemical staining revealed that the co-inoculation of BV2 increased the CD8 T cells' infiltration and the expression of Granzyme B. Mice bearing with BV2-containing ALTS1C1 tumor exhibited a reduced level of circulating myeloid-derived suppressor cells (MDSCs) and an elevated level of CD8 T cells in peripheral blood compared to the ALTS1C1 tumor-bearing group. This study suggests tumor-associated microglia restrict brain tumor development by limiting tumor cell proliferation and inducing T-cell-associated antitumor immunity.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2670-2685"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760570","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

Targeted protein degradation in oncology: novel therapeutic opportunity for solid tumours? 肿瘤靶向蛋白降解：实体瘤的新治疗机会？

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-09-01 Epub Date: 2025-04-23 DOI: 10.1002/1878-0261.70034

Noé Herbel, Sophie Postel-Vinay

引用次数: 0

Aberrant expression of nuclear prothymosin α contributes to epithelial-mesenchymal transition in lung cancer. 核原胸腺酶α的异常表达参与肺癌的上皮-间质转化。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-09-01 Epub Date: 2025-04-21 DOI: 10.1002/1878-0261.70035

Liyun Chen, Chung-Teng Wang, Jia-Ming Chang, Ai-Li Shiau, Gia-Shing Shieh, Yau-Lin Tseng, Yi-Ting Yen, Tang-Hsiu Huang, Li-Hsin Cheng, Yu-Chih Wu, Chao-Liang Wu, Bing-Hua Su, Pensee Wu

{"title":"Aberrant expression of nuclear prothymosin α contributes to epithelial-mesenchymal transition in lung cancer.","authors":"Liyun Chen, Chung-Teng Wang, Jia-Ming Chang, Ai-Li Shiau, Gia-Shing Shieh, Yau-Lin Tseng, Yi-Ting Yen, Tang-Hsiu Huang, Li-Hsin Cheng, Yu-Chih Wu, Chao-Liang Wu, Bing-Hua Su, Pensee Wu","doi":"10.1002/1878-0261.70035","DOIUrl":"10.1002/1878-0261.70035","url":null,"abstract":"Elevated expression of prothymosin α (ProT) is frequently observed in cancers, but the underlying molecular mechanism remains poorly understood. Here, we report the clinical relevance of ProT expression and its correlation with lung cancer progression. We have shown that ProT was highly expressed in early-stage lung cancer, exhibiting nuclear localization; on the contrary, a loss of nuclear ProT expression was detected in late-stage tumor specimens. Furthermore, the expression of nuclear ProT impaired lung cancer cell migration, suppressed TGF-β-induced epithelial-to-mesenchymal transition (EMT)-associated transcription factor expression, and inhibited in vivo tumor metastasis. The suppressive effect of ProT was further found to trigger Smad7 acetylation-dependent deregulation of TGF-β signaling. ProT enhanced Smad7 stability by promoting its lysine acetylation, thereby competing with the binding of Smad2 to the SNAI1, TWIST1, and ZEB1 promoters. Eventually, the binding of Smad7 in the presence of ProT resulted in reduced expression of the EMT transcription factors, leading to the inhibition of TGF-β-induced EMT and tumor metastasis. Collectively, this study unravels the role of ProT in lung cancer progression and highlights the potential of nuclear ProT as an indicator for monitoring tumor development.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2730-2749"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032991","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