IF 6.9 1区医学

Oncogene Pub Date : 2025-07-11 DOI: 10.1038/s41388-025-03485-y

Camille L Duran, Chinmay R Surve, Xianjun Ye, Xiaoming Chen, Yu Lin, Allison S Harney, Yarong Wang, Ved P Sharma, E Richard Stanley, Dianne Cox, John C McAuliffe, David Entenberg, Maja H Oktay, John S Condeelis

{"title":"Targeting CSF-1 signaling between tumor cells and macrophages at TMEM doorways inhibits breast cancer dissemination.","authors":"Camille L Duran, Chinmay R Surve, Xianjun Ye, Xiaoming Chen, Yu Lin, Allison S Harney, Yarong Wang, Ved P Sharma, E Richard Stanley, Dianne Cox, John C McAuliffe, David Entenberg, Maja H Oktay, John S Condeelis","doi":"10.1038/s41388-025-03485-y","DOIUrl":"https://doi.org/10.1038/s41388-025-03485-y","url":null,"abstract":"Tumor cell intravasation is essential for metastatic dissemination, but its exact mechanism is incompletely understood. We have previously shown that in breast cancer, the direct and stable association of a tumor cell expressing Mena, a Tie2hi/VEGFhi macrophage, and a vascular endothelial cell, creates an intravasation portal, called a \"tumor microenvironment of metastasis\" (TMEM) doorway, for tumor cell intravasation, leading to dissemination to distant sites. The density of TMEM doorways, also called TMEM doorway score, is a clinically validated prognostic marker of distant metastasis in breast cancer patients. Although we know that tumor cells utilize TMEM doorway-associated transient vascular openings to intravasate, the precise signaling mechanisms involved in TMEM doorway function are only partially understood. Using two mouse models of breast cancer and an in vitro assay of intravasation, we report that CSF-1 secreted by the TMEM doorway tumor cell stimulates local secretion of VEGF-A from the Tie2hi TMEM doorway macrophage, leading to the dissociation of endothelial junctions between TMEM doorway-associated endothelial cells, supporting tumor cell intravasation. Acute blockade of CSF-1/CSF-1R signaling decreases macrophage VEGF-A secretion as well as TMEM doorway-associated vascular opening, tumor cell trans-endothelial migration, and dissemination. These new insights into signaling events regulating TMEM doorway function should be explored further as treatment strategies for metastatic disease.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 molecular axis hnRNPU/circKCNK2/EDC4/IL-11 aggravates osteolytic bone metastasis of RCC. hnRNPU/circKCNK2/EDC4/IL-11分子轴加重了RCC的溶骨性骨转移。

IF 6.9 1区医学

Oncogene Pub Date : 2025-07-11 DOI: 10.1038/s41388-025-03476-z

Yiqiu Wang, Ding Zhao, Jiayi Lu, Naiqiao Hou, Qianyun Wu, Sian Zhou, Junyao Xu, Wei Xue, Wenguo Cui, Junhua Zheng, Fei Wang, Wei Zhai

{"title":"The molecular axis hnRNPU/circKCNK2/EDC4/IL-11 aggravates osteolytic bone metastasis of RCC.","authors":"Yiqiu Wang, Ding Zhao, Jiayi Lu, Naiqiao Hou, Qianyun Wu, Sian Zhou, Junyao Xu, Wei Xue, Wenguo Cui, Junhua Zheng, Fei Wang, Wei Zhai","doi":"10.1038/s41388-025-03476-z","DOIUrl":"https://doi.org/10.1038/s41388-025-03476-z","url":null,"abstract":"Bone metastasis, which is associated with adverse outcomes, is a serious health concern for renal cell carcinoma (RCC) patients, especially considering the limited therapeutic options. In this study, we investigated the expression profiling of circRNAs in five primary RCC samples and RCC-bone metastases (Bone Met) using high-throughput screening and identified an upregulated circRNA in Bone Met (hsa_circ_0016459, circKCNK2). Notably, overexpression of circKCNK2 could promote osteoclast differentiation and accelerate the destruction of osteolytic bone metastasis by stimulating IL-11 secretion. Additionally, we observed that RCC with a high circKCNK2 expression could benefit from an anti-IL-11 strategy rather than a denosumab-based therapeutic regimen. At the molecular level, circKCNK2 is competitively bound to EDC4 (a scaffold protein of P-bodies). The interaction between circKCNK2 and EDC4α-helical disrupted the combination of DCP1 and DCP2, which weakened the function of P-bodies and resulted in an increased level of IL-11 mRNA and finally activated STAT-3 signaling in osteoclast precursors (OPs). This axis could be blocked with a mutation of EDC4α-helical. Further experiments revealed that increased circKCNK2 production in bone metastases was attributed to decreasing expression of heterogeneous nuclear ribonucleoprotein U (hnRNPU) under an acidic microenvironment. Our findings suggest that circKCNK2 could have a critical role in linking P-bodies to IL-11/STAT-3 signaling. Developing a secure and effective gene delivery system targeted at circKCNK2 is promising for RCC therapy.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Human RNase H2 upregulation counteracts oncogene- and chemotherapy-induced replication stress. 人RNase H2上调可抵消癌基因和化疗诱导的复制应激。

IF 6.9 1区医学

Oncogene Pub Date : 2025-07-10 DOI: 10.1038/s41388-025-03489-8

Rosanna J Wilkins, Abirami Kannan, Siobhan A Plass, Claire Wilson, Richard D W Kelly, Claire H M Tang, Panagiotis Kotsantis, Martin A M Reijns, Aditi Kanhere, Eva Petermann

{"title":"Human RNase H2 upregulation counteracts oncogene- and chemotherapy-induced replication stress.","authors":"Rosanna J Wilkins, Abirami Kannan, Siobhan A Plass, Claire Wilson, Richard D W Kelly, Claire H M Tang, Panagiotis Kotsantis, Martin A M Reijns, Aditi Kanhere, Eva Petermann","doi":"10.1038/s41388-025-03489-8","DOIUrl":"https://doi.org/10.1038/s41388-025-03489-8","url":null,"abstract":"RNase H2 is a heterotrimeric endoribonuclease that resolves RNA:DNA hybrids and genome-embedded ribonucleotides, which are implicated in DNA replication stress and cancer development. Protein and/or mRNA levels of individual RNase H2 subunits are elevated in some cancers, but little is known about the mechanisms or consequences of RNase H2 upregulation. We report that RNase H2 subunits are upregulated at the protein level in response to replication stress induced by oncogenes and chemotherapy drugs in human cancer and non-cancer cell lines. We show that inducible overexpression of the RNASEH2B subunit increases levels of the active RNase H2 heterotrimer. While causing only subtle changes to gene expression, RNASEH2B overexpression is unexpectedly associated with increased RNA:DNA hybrid levels. RNASEH2B overexpression prevents further increases in RNA:DNA hybrid levels by camptothecin or hydroxyurea and reduces replication fork stalling in presence of these drugs. Surprisingly, RNase H2 levels do not strongly impact survival of chemotherapy treatments but appear to have more subtle effects on genome instability and innate immune signalling. In contrast, increased RNase H2 levels in presence of oncogenic HRAS limit not only RAS-induced replication fork stalling but also cell death. Our findings shed new light on the functions of RNase H2 and suggest that upregulation of RNase H2 may be an important aspect of replication stress responses in cancer.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Salvage therapy with allogeneic invariant natural killer cells in a heavily pre-treated germ cell tumor. 同种异体不变性自然杀伤细胞对重度预处理生殖细胞肿瘤的挽救性治疗。

IF 6.9 1区医学

Oncogene Pub Date : 2025-07-10 DOI: 10.1038/s41388-025-03491-0

Benjamin Garmezy, Joseph E Grossman, Jennifer Buell, Thiago Favano, Justin Stebbing, Steven O'Day, Marco A Purbhoo, Dhan Chand, F Anthony Greco

引用次数: 0

The tumor suppressor pRb and its relative p130 are required to maintain murine adult skeletal muscle homeostasis. 肿瘤抑制因子pRb及其相关因子p130是维持小鼠成年骨骼肌稳态所必需的。

IF 6.9 1区医学

Oncogene Pub Date : 2025-07-10 DOI: 10.1038/s41388-025-03487-w

Zhe Jiang, Brittany L Baechler, Huiqin Li, Heta Lad, Giovanni Ciavarra, Yaacov Ben-David, Steven J Burden, Joe Quadrilatero, Eldad Zacksenhaus

{"title":"The tumor suppressor pRb and its relative p130 are required to maintain murine adult skeletal muscle homeostasis.","authors":"Zhe Jiang, Brittany L Baechler, Huiqin Li, Heta Lad, Giovanni Ciavarra, Yaacov Ben-David, Steven J Burden, Joe Quadrilatero, Eldad Zacksenhaus","doi":"10.1038/s41388-025-03487-w","DOIUrl":"https://doi.org/10.1038/s41388-025-03487-w","url":null,"abstract":"The retinoblastoma tumor suppressor pRB is required for skeletal myogenesis but its role in maintenance of post-mitotic skeletal muscle and the contribution, if any, of its relatives, p107 and p130, are largely unknown. Here, we show that targeted deletion of murine Rb in proliferating myoblasts during myogenesis, using a Pax7-Cre deleter line, leads to muscle fiber degeneration, short myotubes with elongated, large nuclei, reduced late muscle marker expression, and fetal death. These defects are recapitulated in primary myoblasts derived from Pax7-Cre:Rbf/f mice, can be ameliorated by inhibition of autophagy in vitro, and are exacerbated in Pax7-Cre:Rbf/f:p107-/- but not Pax7-Cre:Rbf/f:p130-/- double mutant fetuses. In contrast, deletion of Rb on a wildtype or p107-/- background in post-mitotic muscle, via an Mlc1f-Cre deleter line, has no apparent impact on skeletal muscle homeostasis. However, approximately 10% of Mlc1f-Cre:Rbf/f:p130-/- mice, with combined deletion of Rb and p130, exhibit reduced size, wobbly, waddling gait, along with muscle degeneration and dramatic reduction in skeletal muscle mass. The remaining Mlc1f-Cre:Rbf/f:p130-/- mice had near normal posture and muscle mass, but certain muscle areas show extensive central nuclei, while whole muscles express elevated levels of Pax7 and autophagic markers, suggestive of excessive muscle degeneration and regeneration. These mice also display muscle fiber type redistribution accompanied by reduced PGC-1α expression. Thus, continuous pRB and p130 expression is required to maintain skeletal muscle homeostasis and prevent adult muscle degeneration. Moreover, genetic modifiers-yet to be defined-affect the balance between muscle atrophy and regeneration.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Colon cancer cells evade drug action by enhancing drug metabolism. 结肠癌细胞通过增强药物代谢来逃避药物作用。

IF 6.9 1区医学

Oncogene Pub Date : 2025-07-10 DOI: 10.1038/s41388-025-03472-3

Bojie Cong, Teena Thakur, Alejandro Huerta Uribe, Evangelia Stamou, Sindhura Gopinath, Owen Sansom, Oliver Maddocks, Ross Cagan

{"title":"Colon cancer cells evade drug action by enhancing drug metabolism.","authors":"Bojie Cong, Teena Thakur, Alejandro Huerta Uribe, Evangelia Stamou, Sindhura Gopinath, Owen Sansom, Oliver Maddocks, Ross Cagan","doi":"10.1038/s41388-025-03472-3","DOIUrl":"https://doi.org/10.1038/s41388-025-03472-3","url":null,"abstract":"Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. One key reason is the lack of durable therapies that target KRAS-dependent disease, which represents approximately 40% of CRC cases. Here, we use liquid chromatography/mass spectrometry (LC/MS) analyses on Drosophila CRC tumour models to identify multiple metabolites in the glucuronidation pathway-a toxin clearance pathway that impacts most drugs-as upregulated in trametinib-resistant RAS/APC/P53 (\"RAP\") tumours compared to trametinib-sensitive RasG12V single mutant tumours. Genetic inhibition of different steps along the glucuronidation pathway strongly reversed RAP resistance to trametinib; conversely, elevating glucuronidation pathway activity was sufficient to direct trametinib resistance in RasG12V animals. Mechanistically, pairing oncogenic RAS with hyperactive WNT activity strongly elevated PI3K/AKT/GLUT signalling, which in turn directed elevated glucose uptake and glucuronidation; our data also implicate the pentose phosphate pathway in this process. We provide evidence that this mechanism of trametinib resistance is conserved in a KRAS/APC/TP53 mouse CRC tumour organoid model. Finally, we identify two clinically accessible approaches to inhibiting drug glucuronidation: (i) blocking an initial HDAC1-mediated deacetylation step of trametinib with the FDA-approved drug vorinostat; (ii) reducing blood glucose by the alpha-glucosidase inhibitor acarbose. Overall, our observations demonstrate a key mechanism by which oncogenic RAS/WNT activity promotes increased drug clearance in CRC and provides a practical path towards abrogating drug resistance in CRC tumours.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

AVJ16 inhibits lung carcinoma by targeting IGF2BP1. AVJ16通过靶向IGF2BP1抑制肺癌。

IF 6.9 1区医学

Oncogene Pub Date : 2025-07-08 DOI: 10.1038/s41388-025-03449-2

Nadav Wallis, Tehila Gershon, Sojod Shaaby, Froma Oberman, Myriam Grunewald, Deborah Duran, Amandeep Singh, Gilad Vainer, Vladimir S Spiegelman, Arun K Sharma, Joel K Yisraeli

{"title":"AVJ16 inhibits lung carcinoma by targeting IGF2BP1.","authors":"Nadav Wallis, Tehila Gershon, Sojod Shaaby, Froma Oberman, Myriam Grunewald, Deborah Duran, Amandeep Singh, Gilad Vainer, Vladimir S Spiegelman, Arun K Sharma, Joel K Yisraeli","doi":"10.1038/s41388-025-03449-2","DOIUrl":"https://doi.org/10.1038/s41388-025-03449-2","url":null,"abstract":"IGF2BP1 is an oncofoetal RNA binding protein (RBP) expressed in many tumors. Interest has focused of late on the role of RBPs in cancer, although their mechanism of action is not always well understood. Using a newly described small molecule inhibitor of IGF2BP1, termed AVJ16, we have analyzed the effects of this inhibition on RNA binding, RNA expression, and protein expression. AVJ16 treatment downregulates RNAs encoding members of several pro-oncogenic signaling pathways, including Hedgehog, Wnt, and PI3K-Akt, and there is a strong correlation between IGF2BP1 RNA binding, RNA expression, and protein expression. At the cellular level, colony formation, invasion, and spheroid growth are all strongly reduced by exposure to AVJ16, while apoptosis and cell death are enhanced. All of these effects are limited to cells expressing IGF2BP1. In syngeneic LUAD xenografts in mice, IP injection of AVJ16 prevents tumor growth, and incubation with AVJ16 induces cell death in human organoids derived from IGF2BP1-expressing LUADs but not from healthy lung tissue. These results demonstrate that AVJ16 is a promising candidate for targeted therapy directed against tumors expressing IGF2BP1. Please use revised graphical abstract that I uploaded - we found a slight mistake in the original one.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

ALKBH5 suppresses m⁶A mRNA modification of FOXM1 to drive Cetuximab resistance in KRAS-mutant colorectal cancer. ALKBH5抑制FOXM1 m6A mRNA修饰驱动kras突变型结直肠癌西妥昔单抗耐药

IF 6.9 1区医学

Oncogene Pub Date : 2025-07-07 DOI: 10.1038/s41388-025-03490-1

Hu Han, Yan Li, Zhiyi Lin, Xiaoping Ma, Wukui Huang, Cengceng Lu, Rongyan Ma, Rui Han

{"title":"ALKBH5 suppresses m6A mRNA modification of FOXM1 to drive Cetuximab resistance in KRAS-mutant colorectal cancer.","authors":"Hu Han, Yan Li, Zhiyi Lin, Xiaoping Ma, Wukui Huang, Cengceng Lu, Rongyan Ma, Rui Han","doi":"10.1038/s41388-025-03490-1","DOIUrl":"https://doi.org/10.1038/s41388-025-03490-1","url":null,"abstract":"Colorectal cancer (CRC) is a severe health risk, and while Cetuximab is a key treatment, resistance due to KRAS mutations poses a challenge. The role of ALKBH5, often overexpressed in cancers, in KRAS-mutated CRC and its resistance to Cetuximab is not yet fully understood. This research initiates an inquiry from both cellular and animal experimental perspectives, investigating the potential of ALKBH5 to confer resistance to Cetuximab in colorectal cancer cells harboring KRAS mutations. We investigated ALKBH5 expression in clinical samples of CRC with varying responses to Cetuximab and KRAS statuses. Drug-resistant cell lines were developed using incremental drug concentrations, and the effects of ALKBH5 modulation on cell viability and proliferation were assessed using CCK-8 and clonogenic assays. The in vivo impact of ALKBH5 on drug resistance in KRAS-mutant cells was explored. Transcriptome sequencing of ALKBH5 knockdown cells pinpointed genes linked to Cetuximab resistance. We also examined ALKBH5's regulation of FOXM1 m6A methylation with dual-luciferase and MeRIP assays and conducted FOXM1 functional reversal studies, alongside Western blot analysis of Wnt/β-catenin pathway proteins. Elevated ALKBH5 expression is positively correlated with Cetuximab resistance in KRAS-mutant CRC. ALKBH5 confers Cetuximab resistance to CRC cells in a KRAS-mutation-dependent manner in vitro and in vivo. ALKBH5 regulates FOXM1 expression through m6A demethylation, and FOXM1 can reverse Cetuximab resistance in ALKBH5-modulated KRAS-mutated CRC cells. Additionally, FOXM1 influences the sensitivity of KRAS-mutant tumors to Cetuximab by regulating the Wnt/β-catenin pathway. ALKBH5 plays a crucial role in the resistance of KRAS-mutant CRC to Cetuximab by inhibiting the m6A RNA methylation of FOXM1 and suppressing the activation of the Wnt/β-catenin signaling pathway.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Inhibition of tumor growth using A conjugated nanobody that specifically targets c-MYC. 使用特异性靶向c-MYC的共轭纳米体抑制肿瘤生长。

IF 6.9 1区医学

Oncogene Pub Date : 2025-07-06 DOI: 10.1038/s41388-025-03486-x

Yuanyuan Xue, Hao Jiang, Ting Li, Xiaolin Tian, Zelong Miao, Zhaoyun Zong, Wenxi Ding, Yali Wei, Haiteng Deng

{"title":"Inhibition of tumor growth using A conjugated nanobody that specifically targets c-MYC.","authors":"Yuanyuan Xue, Hao Jiang, Ting Li, Xiaolin Tian, Zelong Miao, Zhaoyun Zong, Wenxi Ding, Yali Wei, Haiteng Deng","doi":"10.1038/s41388-025-03486-x","DOIUrl":"https://doi.org/10.1038/s41388-025-03486-x","url":null,"abstract":"The MYC oncogene is a frequently activated oncogene in human cancers, and its high expression is strongly correlated with a poor prognosis. The lack of conventional enzyme-binding sites in MYC poses significant challenges for the development of small-molecule-based therapies to treat MYC-deregulated cancer. In particular, only one transmembrane peptide that targets c-MYC has advanced to early clinical trials, thus highlighting the need of effective and direct approaches for targeting c-MYC in cancer treatment. In this study, we developed a conjugated nanobody (NB) that specifically targets MYC, termed a cell-permeable MYC-targeting nanobody (CPMycNB), via sortase-mediated protein ligation. CPMycNB effectively entered the nucleus and bound to c-MYC, thereby disrupting the c-MYC-MAX interaction. This disruption resulted in the downregulation of c-MYC-targeted genes, activation of apoptotic pathways, and inhibition of cell growth and proliferation in c-MYC-driven tumor cells. Using hydrogen-deuterium exchange mass spectrometry, we found that CPMycNB interacted with the leucine zipper domain of c-MYC. Furthermore, xenograft studies confirmed the therapeutic efficacy of CPMycNB, which significantly reduced tumor size and weight. Our findings highlight the potential of CPMycNB for the treatment of c-MYC-associated malignancies.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Pan-RAS inhibitors and polo-like kinase 1: promising targets in colorectal cancer. 泛ras抑制剂和polo样激酶1：结直肠癌的有希望靶点。

IF 6.9 1区医学

Oncogene Pub Date : 2025-07-04 DOI: 10.1038/s41388-025-03484-z

Priya Jayachandran, Andrew Elliott, Shivani Soni, Francesca Battaglin, Pooja Mittal, Sandra Algaze, Jae Ho Lo, Yan Yang, Karam Ashouri, Evanthia T Roussos Torres, Wu Zhang, Joshua Millstein, Lin Zhang, Jian Yu, Heinz-Josef Lenz

{"title":"Pan-RAS inhibitors and polo-like kinase 1: promising targets in colorectal cancer.","authors":"Priya Jayachandran, Andrew Elliott, Shivani Soni, Francesca Battaglin, Pooja Mittal, Sandra Algaze, Jae Ho Lo, Yan Yang, Karam Ashouri, Evanthia T Roussos Torres, Wu Zhang, Joshua Millstein, Lin Zhang, Jian Yu, Heinz-Josef Lenz","doi":"10.1038/s41388-025-03484-z","DOIUrl":"https://doi.org/10.1038/s41388-025-03484-z","url":null,"abstract":"RAS is an oncogene that is commonly mutated in colorectal cancer (CRC). It has been considered a negative feature both due to its impact on prognosis and due to the shallow interface of oncogenic Ras for therapeutic targeting. Newer pan-Ras inhibitor strategies include improved direct targeting of RAS, blockade of downstream effectors, immunotherapy approaches, and even the inclusion of anti-EGFR drugs. Polo-like Kinase 1 (PLK1) is a serine/threonine protein kinase that controls multiple aspects of the cell-cycle. It is upregulated in CRC and has become an important therapeutic target in KRAS mutant CRC, with several PLK1 inhibitors currently in various phases of development and testing. As with other targeted therapies, resistance remains a problem and combination strategies may be beneficial. This review discusses pan-RAS inhibitors and PLK1 in the context of CRC. It discusses RAS' many roles, its associated pathways and relationship to cancer progression, the current status of existing inhibitors, and future strategies for targeting in cancer therapy. The wide-ranging impacts of RAS provide a basis to better understand and fight against CRC.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

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