Cancer research communications最新文献

{"title":"PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells.","authors":"Zachary A Schaaf, Shu Ning, Amy R Leslie, Masuda Sharifi, Richard Y Gao, James P Maine, Wei Lou, Alan P Lombard, Chengfei Liu, Ai-Ming Yu, Nicholas Mitsiades, Allen C Gao","doi":"10.1158/2767-9764.CRC-24-0339","DOIUrl":"10.1158/2767-9764.CRC-24-0339","url":null,"abstract":"<p><strong>Significance: </strong>Olaparib, a PARP inhibitor, is effective against various cancers, including prostate cancer. However, resistance to olaparib poses a significant challenge. This study uncovers that mitochondrial alterations and PINK1 gene overexpression contribute to this resistance in prostate cancer cells. Enhanced mitochondrial functionality and increased PINK1 expression in olaparib-resistant cells underscore the importance of targeting mitochondrial dynamics and PINK1 to develop more effective treatments for overcoming olaparib resistance in prostate cancer.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"2976-2985"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Region-Based Analyses of Existing Genome-Wide Association Studies Identifies Novel Potential Genetic Susceptibility Regions for Glioma.","authors":"Karen Alpen, Robert J Maclnnis, Claire M Vajdic, John Lai, James G Dowty, Eng-Siew Koh, Elizabeth Hovey, Rosemary Harrup, Tuong L Nguyen, Shuai Li, David Joseph, Geza Benke, Pierre-Antoine Dugué, Melissa C Southey, Graham G Giles, Anna K Nowak, Katharine J Drummond, Daniel F Schmidt, John L Hopper, Miroslaw K Kapuscinski, Enes Makalic","doi":"10.1158/2767-9764.CRC-24-0385","DOIUrl":"10.1158/2767-9764.CRC-24-0385","url":null,"abstract":"<p><strong>Significance: </strong>Further investigation of the potential susceptibility regions identified in our study may lead to a better understanding of glioma genetic risk and the underlying biological etiology of glioma. Our study suggests sex may play a role in genetic susceptibility and highlights the importance of sex-specific analysis in future glioma research.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"2933-2946"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mathematical Modeling Unveils Optimization Strategies for Targeted Radionuclide Therapy of Blood Cancers.","authors":"Maxim Kuznetsov, Vikram Adhikarla, Enrico Caserta, Xiuli Wang, John E Shively, Flavia Pichiorri, Russell C Rockne","doi":"10.1158/2767-9764.CRC-24-0306","DOIUrl":"10.1158/2767-9764.CRC-24-0306","url":null,"abstract":"<p><strong>Significance: </strong>Mathematical modeling yields general principles for optimization of TRT in mouse models of multiple myeloma that can be extrapolated to other cancer models and clinical settings.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"2955-2967"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial Context of Immune Checkpoints as Predictors of Overall Survival in Patients with Resectable Colorectal Cancer Independent of Standard Tumor-Node-Metastasis Stages.","authors":"Hao Kong, Qingxin Yang, Chunwei Wu, Xiangji Wu, Xinrui Yan, Li-Bin Huang, Lu Chen, Zong-Guang Zhou, Ping Wang, Hong Jiang","doi":"10.1158/2767-9764.CRC-24-0270","DOIUrl":"10.1158/2767-9764.CRC-24-0270","url":null,"abstract":"<p><strong>Significance: </strong>The identification of specific spatial patterns of immune checkpoint expression that correlate with overall survival in patients with colon cancer suggests a potential prognostic tool for risk stratification and treatment selection. These findings pave the way for the development of novel therapeutic strategies to enhance antitumor immune responses.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"3025-3035"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ETx-22, a Novel Nectin-4-Directed Antibody-Drug Conjugate, Demonstrates Safety and Potent Antitumor Activity in Low-Nectin-4-Expressing Tumors.","authors":"Marc Lopez, Emerence Crompot, Emmanuelle Josselin, Anne Farina, Marion Rubis, Remy Castellano, Joanna Fares, Maria Wehbe, Yves Collette, Emmanuelle Charafe, Stéphanie Blanchin, François Romagne, Anikó Pálfi, Torsten Hechler, Andreas Pahl, Hatem A Azim, Florence Lhospice, Emilie Mamessier, François Bertucci, Jack Elands, Xavier Préville, Daniel Olive","doi":"10.1158/2767-9764.CRC-24-0176","DOIUrl":"10.1158/2767-9764.CRC-24-0176","url":null,"abstract":"<p><strong>Significance: </strong>ETx-22, a novel ADC combining a tumor nectin-4-specific antibody and an innovative linker to exatecan, demonstrates significant and durable responses in low-target-expressing tumor models that are resistant to MMAE-based EV and has a better toxicity profile. This new ADC has the potential to benefit additional patient populations beyond its current indication.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"2998-3012"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Features of Newly Diagnosed Large B-cell Lymphoma with or without Subsequent Disease Progression.","authors":"Daniel J Landsburg, Jennifer J D Morrissette, Sunita D Nasta, Stefan K Barta, Stephen J Schuster, Elise A Chong, Jakub Svoboda, Ashley Barlev, Adam Bagg, Salvatore F Priore","doi":"10.1158/2767-9764.CRC-24-0337","DOIUrl":"10.1158/2767-9764.CRC-24-0337","url":null,"abstract":"<p><strong>Significance: </strong>Genomic features of LBCL that can be detected by clinical laboratory assays may predict for resistance to first-line immunochemotherapy, as well as support the exploration of genomic features as biomarkers of response to therapies which could be offered to patients who experience disease progression.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"2947-2954"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial Multiomics Reveals Intratumoral Immune Heterogeneity with Distinct Cytokine Networks in Lung Cancer Brain Metastases.","authors":"Gustav Christensson, Matteo Bocci, Julhash U Kazi, Geoffroy Durand, Gustav Lanzing, Kristian Pietras, Hugo Gonzalez Velozo, Catharina Hagerling","doi":"10.1158/2767-9764.CRC-24-0201","DOIUrl":"10.1158/2767-9764.CRC-24-0201","url":null,"abstract":"<p><p>The tumor microenvironment of brain metastases has become a focus in the development of immunotherapeutic drugs. However, countless patients with brain metastasis have not experienced clinical benefit. Thus, understanding the immune cell composition within brain metastases and how immune cells interact with each other and other microenvironmental cell types may be critical for optimizing immunotherapy. We applied spatial whole-transcriptomic profiling with extensive multiregional sampling (19-30 regions per sample) and multiplex IHC on formalin-fixed, paraffin-embedded lung cancer brain metastasis samples. We performed deconvolution of gene expression data to infer the abundances of immune cell populations and inferred spatial relationships from the multiplex IHC data. We also described cytokine networks between immune and tumor cells and used a protein language model to predict drug-target interactions. Finally, we performed deconvolution of bulk RNA data to assess the prognostic significance of immune-metastatic tumor cellular networks. We show that immune cell infiltration has a negative prognostic role in lung cancer brain metastases. Our in-depth multiomics analyses further reveal recurring intratumoral immune heterogeneity and the segregation of myeloid and lymphoid cells into distinct compartments that may be influenced by distinct cytokine networks. By using computational modeling, we identify drugs that may target genes expressed in both tumor core and regions bordering immune infiltrates. Finally, we illustrate the potential negative prognostic role of our immune-metastatic tumor cell networks. Our findings advocate for a paradigm shift from focusing on individual genes or cell types toward targeting networks of immune and tumor cells.</p><p><strong>Significance: </strong>Immune cell signatures are conserved across lung cancer brain metastases, and immune-metastatic tumor cell networks have a prognostic effect, implying that targeting cytokine networks between immune and metastatic tumor cells may generate more precise immunotherapeutic approaches.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"2888-2902"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elraglusib Induces Cytotoxicity via Direct Microtubule Destabilization Independently of GSK3 Inhibition.","authors":"Josh T Coats, Shuyu Li, Tomoyuki U Tanaka, Sudhir Tauro, Calum Sutherland, Adrian T Saurin","doi":"10.1158/2767-9764.CRC-24-0408","DOIUrl":"10.1158/2767-9764.CRC-24-0408","url":null,"abstract":"<p><strong>Significance: </strong>Elraglusib was designed as a GSK3 inhibitor and is currently in clinical trials for several cancers. We show conclusively that the target of elraglusib that leads to cytotoxicity is MTs and not GSK3. This has significant implications for ongoing clinical trials of the compound and will help in understanding off-target side effects, inform future clinical trial design, and facilitate the development of biomarkers to predict response.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"3013-3024"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Red Cell Superoxide Dismutase Activity Is Associated with Cancer Risk: A Hidaka Cohort Study.","authors":"Shin-Ichiro Tanaka, Yoshio Fujioka, Takeshi Tsujino, Tatsuro Ishida, Ken-Ichi Hirata","doi":"10.1158/2767-9764.CRC-24-0301","DOIUrl":"10.1158/2767-9764.CRC-24-0301","url":null,"abstract":"<p><p>Superoxide dismutase (SOD) catalyzes the highly reactive superoxide anion to form hydrogen peroxide, which facilitates cell proliferation and death. We investigated whether red cell SOD (R-SOD) activity is associated with an increased risk of cancer in a Japanese general population. We prospectively analyzed data from 1,921 participants (800 men and 1,121 women; age, 58.7 ± 14.7 years) in a Hidaka cohort study. After a median follow-up period of 10.9 years, 160 participants had developed cancer. The Cox proportional hazards model was used to estimate quartile-specific HRs and 95% confidential intervals (CI) for cancer risk. After adjustment for potential cancer risk factors including age, sex, current smoking habit, alcohol use, physical activities, body mass index, plasma immunoreactive insulin, and non-high-density lipoprotein cholesterol levels, we found a significant association between R-SOD activity and an increased risk of cancer (HR, 1.61; 95% CI, 1.03-2.52; P = 0.037). In analyses conducted separately by sex, a significant association was found in men (HR, 2.49; 95% CI, 1.35-4.59; P = 0.003) but not women (HR, 1.46; 95% CI, 0.70-3.05; P = 0.320). After excluding participants who developed cancer within 5 years of the baseline survey, the association was more evident in men (HR, 4.64; 95% CI, 1.88-11.45; P = 0.001). We found no association with cancer risk in women (HR, 1.01; 95% CI, 0.39-2.65; P = 0.983). Increased R-SOD activities were associated with an increased risk of cancer, particularly in men in this population.</p><p><strong>Significance: </strong>Our study is the first to show that increased R-SOD activity is associated with a significantly higher cancer risk in men but not in women. Antioxidative enzymes such as SOD are essential for maintaining cellular redox balance. Their roles in cancer development and prevention are yet to be fully elucidated.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"2868-2876"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peroxisome Proliferator-Activated Receptor δ Suppresses the Cytotoxicity of CD8+ T Cells by Inhibiting RelA DNA-Binding Activity.","authors":"Bo Cen, Jie Wei, Dingzhi Wang, Raymond N DuBois","doi":"10.1158/2767-9764.CRC-24-0264","DOIUrl":"10.1158/2767-9764.CRC-24-0264","url":null,"abstract":"<p><p>The molecular mechanisms regulating CD8+ cytotoxic T lymphocytes (CTL) are not fully understood. Here, we show that the peroxisome proliferator-activated receptor δ (PPARδ) suppresses CTL cytotoxicity by inhibiting RelA DNA binding. Treatment of ApcMin/+ mice with the PPARδ agonist GW501516 reduced the activation of normal and tumor-associated intestinal CD8+ T cells and increased intestinal adenoma burden. PPARδ knockout or knockdown in CTLs increased their cytotoxicity against colorectal cancer cells, whereas overexpression of PPARδ or agonist treatment decreased it. Correspondingly, perforin, granzyme B, and IFNγ protein and mRNA levels were higher in PPARδ knockout or knockdown CTLs and lower in PPARδ overexpressing or agonist-treated CTLs. Mechanistically, we found that PPARδ binds to RelA, interfering with RelA-p50 heterodimer formation in the nucleus, thereby inhibiting its DNA binding in CTLs. Thus, PPARδ is a critical regulator of CTL effector function. Significance: Here, we provide the first direct evidence that PPARδ plays a critical role in suppressing the immune response against tumors by downregulating RelA DNA-binding activity. This results in decreased expression of perforin, granzyme B, and IFNγ. Thus, PPARδ may serve as a valuable target for developing future cancer immunotherapies.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"2673-2684"},"PeriodicalIF":2.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}