Neoplasia最新文献

{"title":"A synergistic approach for modulating the tumor microenvironment to enhance nano-immunotherapy in sarcomas","authors":"Fotios Mpekris,&nbsp;Myrofora Panagi,&nbsp;Antonia Charalambous,&nbsp;Chrysovalantis Voutouri,&nbsp;Christina Michael,&nbsp;Antonia Papoui,&nbsp;Triantafyllos Stylianopoulos","doi":"10.1016/j.neo.2024.100990","DOIUrl":"https://doi.org/10.1016/j.neo.2024.100990","url":null,"abstract":"<div><p>The lack of properly perfused blood vessels within tumors can significantly hinder the distribution of drugs, leading to reduced treatment effectiveness and having a negative impact on the quality of life of patients with cancer. This problem is particularly pronounced in desmoplastic cancers, where interactions between cancer cells, stromal cells, and the fibrotic matrix lead to tumor stiffness and the compression of most blood vessels within the tumor. To address this issue, two mechanotherapy approaches–mechanotherapeutics and ultrasound sonopermeation–have been employed separately to treat vascular abnormalities in tumors and have reached clinical trials. Here, we performed <em>in vivo</em> studies in sarcomas, to explore the conditions under which these two mechanotherapy strategies could be optimally combined to enhance perfusion and the efficacy of nano-immunotherapy. Our findings demonstrate that combination of the anti-histamine drug ketotifen, as a mechanotherapeutic, and sonopermeation effectively alleviates mechanical forces by decreasing 50 % collagen and hyaluronan levels and thus, reshaping the tumor microenvironment. Furthermore, the combined therapy normalizes the tumor vasculature by increasing two-fold the pericytes coverage. This combination not only improves six times tumor perfusion but also enhances drug delivery. As a result, blood vessel functionality is enhanced, leading to increased infiltration by 40 % of immune cells (CD4⁺ and CD8⁺ T-cells) and improving the antitumor efficacy of Doxil nanomedicine and anti-PD-1 immunotherapy. In conclusion, our research underscores the unique and synergistic potential of combining mechanotherapeutics and sonopermeation. Both approaches are undergoing clinical trials to enhance cancer therapy and have the potential to significantly improve nano-immunotherapy in sarcomas.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"51 ","pages":"Article 100990"},"PeriodicalIF":4.8,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000277/pdfft?md5=248235ac2f092469f099925770d1fcc4&pid=1-s2.0-S1476558624000277-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140187791","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}

{"title":"Disease burden and projection of total and early-onset colorectal cancer in Gulf cooperation council countries from 1990 to 2019","authors":"Majed Ramadan ,&nbsp;Hanin Ghamdi ,&nbsp;Doaa Aboalola ,&nbsp;Noha Alorainan ,&nbsp;Ragad Alsalmi ,&nbsp;Ahmed Afash ,&nbsp;Albaraa Hariri ,&nbsp;Atheer Alboloshi ,&nbsp;Alaa Samkari ,&nbsp;Rawiah Alsiary","doi":"10.1016/j.neo.2024.100988","DOIUrl":"https://doi.org/10.1016/j.neo.2024.100988","url":null,"abstract":"<div><h3>Background</h3><p>Early-onset colorectal cancer (EO-CRC) incidence and prevalence trends in the rise in high income countries, such as the Gulf Cooperation Council (GCC) countries. The study aimed to offer an up-to-date assessment of the overall burden of CRC, and EO-CRC in GCC countries and project its incidence and mortality in 2030.</p></div><div><h3>Method</h3><p>The prevalence, incidence, mortality, years of life lived with disability (YLDs), and disability-adjusted life years (DALYs) of CRC were obtained from the Global Burden of Disease (GBD) Study 2019. The incidence and mortality of CRC, and EO-CRC up to 2030 were predicted.</p></div><div><h3>Results</h3><p>All GCC countries showed a higher annual average percentage changes (AAPC) AAPC incidence rate for EO-CRC compared to CRC. In Saudi Arabia the number of CRC cases has increased from 1990 1484.57; (95 % UI 1987.98,1083.86) 11.4-fold-increase to 16991.83; (95 % UI 21754.79,12892.12) in 2019. In 2030, the total incidence cases of CRC for the six Gulf countries are expected to reach 13,339 thousand, primarily driven by Saudi Arabia with 7,910.19 cases. In 2030, the CRC mortality rate is projected to be 7,647 cases, with nearly 57 % of CRC mortality cases anticipated in Saudi Arabia.</p></div><div><h3>Conclusion</h3><p>This study sheds light on the alarming rise in CRC and EO-CRC across Gulf countries from 1990 to 2019, emphasizing Saudi Arabia's significant burden. It projects a concerning increase in CRC incidence and mortality by 2030, primarily in Saudi Arabia, and highlights the need for immediate public health interventions.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"51 ","pages":"Article 100988"},"PeriodicalIF":4.8,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000253/pdfft?md5=2800fbb879f8fa87804346e52180016c&pid=1-s2.0-S1476558624000253-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140163060","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}

{"title":"Dihydroartemisinin, a potential PTGS1 inhibitor, potentiated cisplatin-induced cell death in non-small cell lung cancer through activating ROS-mediated multiple signaling pathways","authors":"Lianli Ni ,&nbsp;Xinping Zhu ,&nbsp;Qi Zhao ,&nbsp;Yiwei Shen ,&nbsp;Lu Tao ,&nbsp;Ji Zhang ,&nbsp;Han Lin ,&nbsp;Weishan Zhuge ,&nbsp;Young-Chang Cho ,&nbsp;Ri Cui ,&nbsp;Wangyu Zhu","doi":"10.1016/j.neo.2024.100991","DOIUrl":"https://doi.org/10.1016/j.neo.2024.100991","url":null,"abstract":"<div><p>Dihydroartemisinin (DHA) exerts an anti-tumor effect in multiple cancers, however, the molecular mechanism of DHA and whether DHA facilitates the anti-tumor efficacy of cisplatin in non-small cell lung cancer (NSCLC) are unclear. Here, we found that DHA potentiated the anti-tumor effects of cisplatin in NSCLC cells by stimulating reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress, C-Jun-amino-terminal kinase (JNK) and p38 MAPK signaling pathways both in <em>vitro</em> and in <em>vivo</em>. Of note, we demonstrated for the first time that DHA inhibits prostaglandin G/H synthase 1 (PTGS1) expression, resulting in enhanced ROS production. Importantly, silencing PTGS1 sensitized DHA-induced cell death by increasing ROS production and activating ER-stress, JNK and p38 MAPK signaling pathways. In summary, our findings provided new experimental basis and therapeutic prospect for the combined therapy with DHA and cisplatin in some NSCLC patients.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"51 ","pages":"Article 100991"},"PeriodicalIF":4.8,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000289/pdfft?md5=9d9621fe5697150db7a70a6aa34c9a8e&pid=1-s2.0-S1476558624000289-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140163961","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}

{"title":"Corrigendum to “Androgen receptor degraders overcome common resistance mechanisms developed during prostate cancer treatment” [Neoplasia, Volume 22, Issue 2 (2020) 111–119]","authors":"Steven Kregel ,&nbsp;Chao Wang ,&nbsp;Xin Han ,&nbsp;Lanbo Xiao ,&nbsp;Ester Fernandez-Salas ,&nbsp;Pushpinder Bawa ,&nbsp;Brooke L. McCollum ,&nbsp;Kari Wilder-Romans ,&nbsp;Ingrid J. Apel ,&nbsp;Xuhong Cao ,&nbsp;Corey Speers ,&nbsp;Shaomeng Wang ,&nbsp;Arul M. Chinnaiyan","doi":"10.1016/j.neo.2024.100986","DOIUrl":"https://doi.org/10.1016/j.neo.2024.100986","url":null,"abstract":"","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"51 ","pages":"Article 100986"},"PeriodicalIF":4.8,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S147655862400023X/pdfft?md5=5ef5169bb15da24af05d45a36eb6a114&pid=1-s2.0-S147655862400023X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140134617","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}

{"title":"PIK3R1 fusion drives chemoresistance in ovarian cancer by activating ERK1/2 and inducing rod and ring-like structures","authors":"Heidi Rausio ,&nbsp;Alejandra Cervera ,&nbsp;Vanina D. Heuser ,&nbsp;Gun West ,&nbsp;Jaana Oikkonen ,&nbsp;Elena Pianfetti ,&nbsp;Marta Lovino ,&nbsp;Elisa Ficarra ,&nbsp;Pekka Taimen ,&nbsp;Johanna Hynninen ,&nbsp;Rainer Lehtonen ,&nbsp;Sampsa Hautaniemi ,&nbsp;Olli Carpén ,&nbsp;Kaisa Huhtinen","doi":"10.1016/j.neo.2024.100987","DOIUrl":"https://doi.org/10.1016/j.neo.2024.100987","url":null,"abstract":"<div><p>Gene fusions are common in high-grade serous ovarian cancer (HGSC). Such genetic lesions may promote tumorigenesis, but the pathogenic mechanisms are currently poorly understood. Here, we investigated the role of a PIK3R1-CCDC178 fusion identified from a patient with advanced HGSC. We show that the fusion induces HGSC cell migration by regulating ERK1/2 and increases resistance to platinum treatment. Platinum resistance was associated with rod and ring-like cellular structure formation. These structures contained, in addition to the fusion protein, CIN85, a key regulator of PI3K-AKT-mTOR signaling. Our data suggest that the fusion-driven structure formation induces a previously unrecognized cell survival and resistance mechanism, which depends on ERK1/2-activation.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"51 ","pages":"Article 100987"},"PeriodicalIF":4.8,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000241/pdfft?md5=f8e2bd5c24ada23b62b40db1984af77e&pid=1-s2.0-S1476558624000241-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140134618","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}

{"title":"Advancing glioblastoma treatment by targeting metabolism","authors":"Jinyi Zhao ,&nbsp;Xuemei Ma ,&nbsp;Peixian Gao ,&nbsp;Xueqi Han ,&nbsp;Pengxiang Zhao ,&nbsp;Fei Xie ,&nbsp;Mengyu Liu","doi":"10.1016/j.neo.2024.100985","DOIUrl":"https://doi.org/10.1016/j.neo.2024.100985","url":null,"abstract":"<div><p>Alterations in cellular metabolism are important hallmarks of glioblastoma(GBM). Metabolic reprogramming is a critical feature as it meets the higher nutritional demand of tumor cells, including proliferation, growth, and survival. Many genes, proteins, and metabolites associated with GBM metabolism reprogramming have been found to be aberrantly expressed, which may provide potential targets for cancer treatment. Therefore, it is becoming increasingly important to explore the role of internal and external factors in metabolic regulation in order to identify more precise therapeutic targets and diagnostic markers for GBM. In this review, we define the metabolic characteristics of GBM, investigate metabolic specificities such as targetable vulnerabilities and therapeutic resistance, as well as present current efforts to target GBM metabolism to improve the standard of care.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"51 ","pages":"Article 100985"},"PeriodicalIF":4.8,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000228/pdfft?md5=8db8e44cf2fcb3f3b9420c8035568d7f&pid=1-s2.0-S1476558624000228-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140113167","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}

{"title":"ST6GAL1 is associated with poor response to chemoradiation in rectal cancer","authors":"Mary Smithson ,&nbsp;Sameer Al Diffalha ,&nbsp;Regina K. Irwin ,&nbsp;Gregory Williams ,&nbsp;M. Chandler McLeod ,&nbsp;Vivek Somasundaram ,&nbsp;Susan L. Bellis ,&nbsp;Karin M. Hardiman","doi":"10.1016/j.neo.2024.100984","DOIUrl":"https://doi.org/10.1016/j.neo.2024.100984","url":null,"abstract":"<div><h3>Introduction</h3><p>Colorectal cancer is the third most common cause of cancer death. Rectal cancer makes up a third of all colorectal cases. Treatment for locally advanced rectal cancer includes chemoradiation followed by surgery. We have previously identified ST6GAL1 as a cause of resistance to chemoradiation <em>in vitro</em> and hypothesized that it would be correlated with poor response in human derived models and human tissues.</p></div><div><h3>Methods</h3><p>Five organoid models were created from primary human rectal cancers and ST6GAL1 was knocked down via lentivirus transduction in one model. ST6GAL1 and Cleaved Caspase-3 (CC3) were assessed after chemoradiation via immunostaining. A tissue microarray (TMA) was created from twenty-six patients who underwent chemoradiation and had pre- and post-treatment specimens of rectal adenocarcinoma available at our institution. Immunohistochemistry was performed for ST6GAL1 and percent positive cancer cell staining was assessed and correlation with pathological grade of response was measured.</p></div><div><h3>Results</h3><p>Organoid models were treated with chemoradiation and both ST6GAL1 mRNA and protein significantly increased after treatment. The organoid model targeted with ST6GAL1 knockdown was found to have increased CC3 after treatment. In the tissue microarray, 42 percent of patient samples had an increase in percent tumor cell staining for ST6GAL1 after treatment. Post-treatment percent staining was associated with a worse grade of treatment response (p = 0.01) and increased staining post-treatment compared to pre-treatment was also associated with a worse response (p = 0.01).</p></div><div><h3>Conclusion</h3><p>ST6GAL1 is associated with resistance to treatment in human rectal cancer and knockdown in an organoid model abrogated resistance to apoptosis caused by chemoradiation.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"51 ","pages":"Article 100984"},"PeriodicalIF":4.8,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000216/pdfft?md5=e64d225a0ea5be563852b2212ff505da&pid=1-s2.0-S1476558624000216-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095641","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}

{"title":"IL-6 facilitates cross-talk between epithelial cells and tumor- associated macrophages in Helicobacter pylori-linked gastric carcinogenesis","authors":"Bingting Yu ,&nbsp;Danny de Vos ,&nbsp;Xiaopei Guo ,&nbsp;SanFei Peng ,&nbsp;Wenjie Xie ,&nbsp;Maikel P. Peppelenbosch ,&nbsp;Yang Fu ,&nbsp;Gwenny M. Fuhler","doi":"10.1016/j.neo.2024.100981","DOIUrl":"https://doi.org/10.1016/j.neo.2024.100981","url":null,"abstract":"<div><h3>Purpose</h3><p><em>Helicobacter pylori (H. pylori)</em> is a significant risk factor for development of gastric cancer (GC), one of the deadliest malignancies in the world. However, the mechanism by which <em>H. pylori</em> induces gastric oncogenesis remains unclear. Here, we investigated the function of IL-6 in gastric oncogenesis and macrophage-epithelial cell interactions.</p></div><div><h3>Methods</h3><p>We analyzed publicly available datasets to investigate the expression of <em>IL-6</em> and infiltration of M2 macrophages in GC tissues, and determine the inter-cellular communication in the context of IL-6. Human gastric epithelial and macrophage cell lines (GES-1 and THP-1-derived macrophages, respectively) were used in mono- and co-culture experiments to investigate autocrine-and paracrine induction of IL-6 expression in response to <em>H. pylori</em> or IL-6 stimulation.</p></div><div><h3>Results</h3><p>We found that IL-6 is highly expressed in GC and modulates survival. M2 macrophage infiltration is predominant in GC and drives an IL-6 mediated communication with gastric epithelium cells. <em>In vitro</em>, IL-6 triggers its own expression in GES-1 and THP-1-derived macrophages cells. In addition, these cell lines are able to upregulate each other's IL-6 levels in an autocrine fashion, which is enhanced by <em>H. pylori</em> stimulation.</p></div><div><h3>Conclusion</h3><p>This study indicates that IL-6 in the tumor microenvironment is essential for intercellular communication. We show that <em>H. pylori</em> enhances an IL-6-driven autocrine and paracrine positive feedback loop between macrophages and gastric epithelial cells, which may contribute to gastric carcinogenesis.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"50 ","pages":"Article 100981"},"PeriodicalIF":4.8,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000186/pdfft?md5=66f78ac2b09e0475ccaa1d5ae71a143c&pid=1-s2.0-S1476558624000186-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139992903","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}

{"title":"Glypican-1-targeted antibody–drug conjugate inhibits the growth of glypican-1-positive glioblastoma","authors":"Shun Uchida ,&nbsp;Satoshi Serada ,&nbsp;Yuji Suzuki ,&nbsp;Eiji Funajima ,&nbsp;Kei Kitakami ,&nbsp;Kazumasa Dobashi ,&nbsp;Satomi Tamatani ,&nbsp;Yuichi Sato ,&nbsp;Takaaki Beppu ,&nbsp;Kuniaki Ogasawara ,&nbsp;Testuji Naka","doi":"10.1016/j.neo.2024.100982","DOIUrl":"https://doi.org/10.1016/j.neo.2024.100982","url":null,"abstract":"<div><p>Glioblastoma is the deadliest form of brain tumor. The presence of the blood–brain barrier (BBB) significantly hinders chemotherapy, necessitating the development of innovative treatment options for this tumor. This report presents the <em>in vitro</em> and <em>in vivo</em> efficacy of an antibody–drug conjugate (ADC) that targets glypican-1 (GPC1) in glioblastoma. The GPC1-ADC was created by conjugating a humanized anti-GPC1 antibody (clone T2) with monomethyl auristatin E (MMAE) <em>via</em> maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl linkers. Immunohistochemical staining analysis of a glioblastoma tissue microarray revealed that GPC1 expression was elevated in more than half of the cases. GPC1-ADC, when bound to GPC1, was efficiently and rapidly internalized in glioblastoma cell lines. It inhibited the growth of GPC1-positive glioma cell lines by inducing cell cycle arrest in the G2/M phase and triggering apoptosis <em>in vitro</em>. We established a heterotopic xenograft model by subcutaneously implanting KALS-1 and administered GPC1-ADC intravenously. GPC1-ADC significantly inhibited tumor growth and increased the number of mitotic cells. We also established an orthotopic xenograft model by intracranially implanting luciferase-transfected KS-1-Luc#19. After injecting Evans blue and resecting brain tissues, dye leakage was observed in the implantation area, confirming BBB disruption. We administered GPC1-ADC intravenously and measured the luciferase activity using an <em>in vivo</em> imaging system. GPC1-ADC significantly inhibited tumor growth and extended survival. In conclusion, GPC1-ADC demonstrated potent intracranial activity against GPC1-positive glioblastoma in an orthotopic xenograft model. These results indicate that GPC1-ADC could represent a groundbreaking new therapy for treating glioblastoma beyond the BBB.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"50 ","pages":"Article 100982"},"PeriodicalIF":4.8,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000198/pdfft?md5=30ea273849b18d645bc33f865a23dfba&pid=1-s2.0-S1476558624000198-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139986841","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}

{"title":"Identification of recurrent BRAF non-V600 mutations in intraductal carcinoma of the prostate in Chinese populations","authors":"Jing Hu ,&nbsp;Xinyi Chen ,&nbsp;Feifei Sun ,&nbsp;Lili Liu ,&nbsp;Long Liu ,&nbsp;Zimeng Yang ,&nbsp;Hanwen Zhang ,&nbsp;Zeyuan Yu ,&nbsp;Ru Zhao ,&nbsp;Yueyao Wang ,&nbsp;Hui Liu ,&nbsp;Xiaorong Yang ,&nbsp;Fusheng Sun ,&nbsp;Bo Han","doi":"10.1016/j.neo.2024.100983","DOIUrl":"https://doi.org/10.1016/j.neo.2024.100983","url":null,"abstract":"<div><p>While <em>BRAF</em> alterations have been established as a driver in various solid malignancies, the characterization of <em>BRAF</em> alterations in prostate cancer (PCa) has not been thoroughly interrogated. By bioinformatics analysis, we first found that <em>BRAF</em> alterations were associated with advanced PCa and exhibited mutually exclusive pattern with ERG alteration across multiple cohorts. Of the most interest, recurrent non-V600 <em>BRAF</em> mutations were found in 3 of 21 (14.3 %) PCa patients demonstrating IDC-P morphology. Furthermore, experimental overexpression of <em>BRAF^K601E</em> and <em>BRAF^L597R</em> exhibited emergence of oncogenic phenotypes with intensified MAPK signaling <em>in vitro</em>, which could be targeted by MEK inhibitors<em>.</em> Comparison of the incidence of <em>BRAF</em> alterations in IDC-P between western and Chinese ancestry revealed an increased prevalence in the Chinese population. The <em>BRAF</em> mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 <em>BRAF</em> mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"50 ","pages":"Article 100983"},"PeriodicalIF":4.8,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000204/pdfft?md5=ffc2fe277ab8b3fe511b61dba80b747a&pid=1-s2.0-S1476558624000204-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975672","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}