Cancer Communications最新文献

{"title":"SERPINE2 promotes liver cancer metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation","authors":"Shiyu Zhang, Xing Jia, Haojiang Dai, Xingxin Zhu, Wenfeng Song, Suchen Bian, Hao Wu, Shinuo Chen, Yangbo Tang, Junran Chen, Cheng Jin, Mengqiao Zhou, Haiyang Xie, Shusen Zheng, Penghong Song","doi":"10.1002/cac2.12527","DOIUrl":"10.1002/cac2.12527","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Liver cancer is a malignancy with high morbidity and mortality rates. Serpin family E member 2 (SERPINE2) has been reported to play a key role in the metastasis of many tumors. In this study, we aimed to investigate the potential mechanism of SERPINE2 in liver cancer metastasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Cancer Genome Atlas database (TCGA), including DNA methylation and transcriptome sequencing data, was utilized to identify the crucial oncogene associated with DNA methylation and cancer progression in liver cancer. Data from the TCGA and RNA sequencing for 94 pairs of liver cancer tissues were used to explore the correlation between SERPINE2 expression and clinical parameters of patients. DNA methylation sequencing was used to detect the DNA methylation levels in liver cancer tissues and cells. RNA sequencing, cytokine assays, immunoprecipitation (IP) and mass spectrometry (MS) assays, protein stability assays, and ubiquitination assays were performed to explore the regulatory mechanism of SERPINE2 in liver cancer metastasis. Patient-derived xenografts and tumor organoid models were established to determine the role of SERPINE2 in the treatment of liver cancer using sorafenib.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Based on the public database screening, SERPINE2 was identified as a tumor promoter regulated by DNA methylation. SERPINE2 expression was significantly higher in liver cancer tissues and was associated with the dismal prognosis in patients with liver cancer. SERPINE2 promoted liver cancer metastasis by enhancing cell pseudopodia formation, cell adhesion, cancer-associated fibroblast activation, extracellular matrix remodeling, and angiogenesis. IP/MS assays confirmed that SERPINE2 activated epidermal growth factor receptor (EGFR) and its downstream signaling pathways by interacting with EGFR. Mechanistically, SERPINE2 inhibited EGFR ubiquitination and maintained its protein stability by competing with the E3 ubiquitin ligase, c-Cbl. Additionally, EGFR was activated in liver cancer cells after sorafenib treatment, and SERPINE2 knockdown-induced EGFR downregulation significantly enhanced the therapeutic efficacy of sorafenib against liver cancer. Furthermore, we found that SERPINE2 knockdown also had a sensitizing effect on lenvatinib treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SERPINE2 promoted liver cancer metastasis by preventing EGFR degradation via c-Cbl-mediated ubiquitination, suggesting that inhibition of the SERPINE2-EGFR axis may be a potenti","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 3","pages":"384-407"},"PeriodicalIF":16.2,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NAT10-mediated ac4C-modified ANKZF1 promotes tumor progression and lymphangiogenesis in clear-cell renal cell carcinoma by attenuating YWHAE-driven cytoplasmic retention of YAP1","authors":"Daojia Miao,&nbsp;Jian Shi,&nbsp;Qingyang Lv,&nbsp;Diaoyi Tan,&nbsp;Chuanyi Zhao,&nbsp;Zhiyong Xiong,&nbsp;Xiaoping Zhang","doi":"10.1002/cac2.12523","DOIUrl":"10.1002/cac2.12523","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lymphatic metastasis is one of the most common metastatic routes and indicates a poor prognosis in clear-cell renal cell carcinoma (ccRCC). N-acetyltransferase 10 (NAT10) is known to catalyze N4-acetylcytidine (ac⁴C) modification of mRNA and participate in many cellular processes. However, its role in the lymphangiogenic process of ccRCC has not been reported. This study aimed to elucidate the role of NAT10 in ccRCC lymphangiogenesis, providing valuable insights into potential therapeutic targets for intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>ac⁴C modification and NAT10 expression levels in ccRCC were assessed using public databases and clinical samples. Functional investigations involved manipulating NAT10 expression in cellular and mouse models to study its role in ccRCC. Mechanistic insights were gained through a combination of RNA sequencing, mass spectrometry, co-immunoprecipitation, RNA immunoprecipitation, immunofluorescence, and site-specific mutation analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that ac⁴C modification and NAT10 expression levels increased in ccRCC. NAT10 promoted tumor progression and lymphangiogenesis of ccRCC by enhancing the nuclear import of Yes1-associated transcriptional regulator (YAP1). Subsequently, we identified ankyrin repeat and zinc finger peptidyl tRNA hydrolase 1 (ANKZF1) as the functional target of NAT10, and its upregulation in ccRCC was caused by NAT10-mediated ac⁴C modification. Mechanistic analyses demonstrated that ANKZF1 interacted with tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (YWHAE) to competitively inhibit cytoplasmic retention of YAP1, leading to transcriptional activation of pro-lymphangiogenic factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results suggested a pro-cancer role of NAT10-mediated acetylation in ccRCC and identified the NAT10/ANKZF1/YAP1 axis as an under-reported pathway involving tumor progression and lymphangiogenesis in ccRCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 3","pages":"361-383"},"PeriodicalIF":16.2,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel strategy for treating oncogene-mutated tumors by targeting tumor microenvironment and synergistically enhancing anti-PD-1 immunotherapy","authors":"Yingqiang Liu,&nbsp;Linjiang Tong,&nbsp;Mengge Zhang,&nbsp;Qi Zhang,&nbsp;Qiupei Liu,&nbsp;Fang Feng,&nbsp;Yan Li,&nbsp;Mengzhen Lai,&nbsp;Haotian Tang,&nbsp;Yi Chen,&nbsp;Meiyu Geng,&nbsp;Wenhu Duan,&nbsp;Jian Ding,&nbsp;Hua Xie","doi":"10.1002/cac2.12521","DOIUrl":"10.1002/cac2.12521","url":null,"abstract":"&lt;p&gt;Oncogenes are critical factors in tumorigenesis of diverse cancer types and play essential roles in tumor immune escape. Mutations in Kirsten rat sarcoma viral oncogene homolog (&lt;i&gt;KRAS&lt;/i&gt;) and epidermal growth factor receptor (&lt;i&gt;EGFR&lt;/i&gt;) are among the most frequent gain-of-function alterations [&lt;span&gt;1&lt;/span&gt;]. After many years of in-depth research, inhibitors targeting &lt;i&gt;EGFR&lt;/i&gt; or &lt;i&gt;KRAS&lt;/i&gt; mutations have been successfully developed, however, their clinical benefit is relatively limited, and they will inevitably encounter the challenge of drug resistance. The emergence of resistance is attributed to secondary mutations in driver genes and other complicated factors. It is worth noting that approved treatment strategies are currently lacking for tumors with different types of &lt;i&gt;KRAS&lt;/i&gt; or &lt;i&gt;EGFR&lt;/i&gt; mutations, including &lt;i&gt;KRAS&lt;sup&gt;G12D&lt;/sup&gt;&lt;/i&gt;, &lt;i&gt;KRAS&lt;sup&gt;G13D&lt;/sup&gt;&lt;/i&gt;, and &lt;i&gt;EGFR&lt;sup&gt;C797S&lt;/sup&gt;&lt;/i&gt; mutations that are common in tumors [&lt;span&gt;2&lt;/span&gt;]. Additionally, oncogene mutations could trigger a cascade of tumor microenvironment changes, ultimately resulting in tumor progression or resistance to programmed death-1 (PD-1) antibody therapy [&lt;span&gt;3, 4&lt;/span&gt;]. SYHA1813, a novel vascular endothelial growth factor receptor (VEGFR) and colony-stimulating factor 1 receptor (CSF1R) dual inhibitor, exhibited potent preclinical anti-glioma activity by inhibiting angiogenesis and promoting tumor immunity and showed promising efficacy in an ongoing clinical study (ChiCTR2100045380) [&lt;span&gt;5, 6&lt;/span&gt;]. Here, we determined SYHA1813's antitumor activity in tumor models bearing &lt;i&gt;KRAS&lt;/i&gt; or &lt;i&gt;EGFR&lt;/i&gt; mutations.&lt;/p&gt;&lt;p&gt;We first examined the effects of SYHA1813 against cell line-derived xenograft (CDX) tumor models containing &lt;i&gt;KRAS&lt;sup&gt;G12C&lt;/sup&gt;&lt;/i&gt; mutation (NCI-H358 lung cancer), &lt;i&gt;KRAS&lt;sup&gt;G12D&lt;/sup&gt;&lt;/i&gt; mutation (PANC-1 pancreatic cancer) and wild-type &lt;i&gt;KRAS&lt;/i&gt; (&lt;i&gt;KRAS&lt;sup&gt;WT&lt;/sup&gt;&lt;/i&gt;) (HT-29 colorectal cancer). The results demonstrated that oral administration of SYHA1813 at a dose of 10 mg/kg significantly reduced tumor growth in the NCI-H358 xenograft model, with comparable efficacy to the US Food and Drug Administration (FDA) approved KRAS&lt;sup&gt;G12C&lt;/sup&gt; inhibitor sotorasib (AMG510) (Figure 1A). SYHA1813 treatment also resulted in tumor regression in PANC-1 and HT-29 xenograft models (Figure 1B-C). No significant body weight loss was observed in all groups (Supplementary Figure S1). Moreover, considering the emergence of drug resistance as a significant challenge of AMG510, we established a drug resistance model of AMG510 (designated as AMG510R). We found that although AMG510 exhibited attenuated efficacy against the AMG510R model compared to the NCI-H358 model, SYHA1813 could still suppress the growth of drug-resistant tumors at the same dose (Figure 1D). Furthermore, SYHA1813 was evaluated in two patient-derived xenograft (PDX) models, including gastric tumor model GC-1-005 (&lt;i&gt;KRAS&lt;sup&gt;G13D&lt;/sup&gt;&lt;/i&gt;) and colorect","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 3","pages":"438-442"},"PeriodicalIF":16.2,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12521","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139711572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover Image, Volume 44, Issue 1","authors":"Monika Raab,&nbsp;Izabela Kostova,&nbsp;Samuel Peña-Llopis,&nbsp;Daniela Fietz,&nbsp;Monika Kressin,&nbsp;Seyed Mohsen Aberoumandi,&nbsp;Evelyn Ullrich,&nbsp;Sven Becker,&nbsp;Mourad Sanhaji,&nbsp;Klaus Strebhardt","doi":"10.1002/cac2.12522","DOIUrl":"https://doi.org/10.1002/cac2.12522","url":null,"abstract":"<p>The cover image is based on the Original Article <i>Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of highgrade serous ovarian cancer</i> by Monika Raab et al., https://doi.org/10.1002/cac2.12511.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139695464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy","authors":"Bin Song,&nbsp;Ping Yang,&nbsp;Shuyu Zhang","doi":"10.1002/cac2.12520","DOIUrl":"10.1002/cac2.12520","url":null,"abstract":"<p>Cancer is a leading cause of death worldwide. Targeted therapies aimed at key oncogenic driver mutations in combination with chemotherapy and radiotherapy as well as immunotherapy have benefited cancer patients considerably. Tumor protein p53 (<i>TP53</i>), a crucial tumor suppressor gene encoding p53, regulates numerous downstream genes and cellular phenotypes in response to various stressors. The affected genes are involved in diverse processes, including cell cycle arrest, DNA repair, cellular senescence, metabolic homeostasis, apoptosis, and autophagy. However, accumulating recent studies have continued to reveal novel and unexpected functions of p53 in governing the fate of tumors, for example, functions in ferroptosis, immunity, the tumor microenvironment and microbiome metabolism. Among the possibilities, the evolutionary plasticity of p53 is the most controversial, partially due to the dizzying array of biological functions that have been attributed to different regulatory mechanisms of p53 signaling. Nearly 40 years after its discovery, this key tumor suppressor remains somewhat enigmatic. The intricate and diverse functions of p53 in regulating cell fate during cancer treatment are only the tip of the iceberg with respect to its equally complicated structural biology, which has been painstakingly revealed. Additionally, <i>TP53</i> mutation is one of the most significant genetic alterations in cancer, contributing to rapid cancer cell growth and tumor progression. Here, we summarized recent advances that implicate altered p53 in modulating the response to various cancer therapies, including chemotherapy, radiotherapy, and immunotherapy. Furthermore, we also discussed potential strategies for targeting p53 as a therapeutic option for cancer.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 3","pages":"297-360"},"PeriodicalIF":16.2,"publicationDate":"2024-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12520","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139689067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AP4 induces JNK1 and a miR-22-3p/FOSL1 feed-forward loop to activate AP-1 and promote colorectal cancer metastasis","authors":"Jinjiang Chou,&nbsp;Markus Kaller,&nbsp;Matjaz Rokavec,&nbsp;Fangteng Liu,&nbsp;Heiko Hermeking","doi":"10.1002/cac2.12514","DOIUrl":"10.1002/cac2.12514","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Colorectal cancer (CRC) is the third most deadly cancer worldwide [&lt;span&gt;1&lt;/span&gt;]. The mortality of CRC has remained high due to limited treatment options for metastatic CRC (mCRC) [&lt;span&gt;2&lt;/span&gt;]. Epithelial-mesenchymal transition (EMT) is an important contributor to mCRC [&lt;span&gt;2&lt;/span&gt;]. The c-MYC proto-oncogene (MYC)-induced transcription factor AP4 (TFAP4/AP4) is a driver of EMT, thereby presumably facilitates mCRC [&lt;span&gt;3, 4&lt;/span&gt;]. The mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway has been implicated in the regulation of EMT and mCRC [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Here, we analyzed whether AP4 regulates components of the MAPK/JNK/AP-1 pathway after MYC activation using CRC cells rendered &lt;i&gt;AP4&lt;/i&gt;-deficient by a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) approach. The detailed methods are shown in the Supplementary file. First, we grouped MYC-induced changes in mRNA expression observed in the CRC cell line DLD-1 &lt;i&gt;AP4&lt;/i&gt; wild-type 1/pRTR-&lt;i&gt;c-MYC&lt;/i&gt;-VSV (&lt;i&gt;AP4&lt;/i&gt;-WT1 DLD-1/pRTR-&lt;i&gt;c&lt;/i&gt;-&lt;i&gt;MYC-&lt;/i&gt;VSV) into 6 non-overlapping expression clusters (Supplementary Figure S1A, left), with cluster 1 representing mRNAs down-regulated, and clusters 2-6 representing different patterns of mRNA up-regulated after MYC activation. MAPK signaling pathway components were strongly over-represented in cluster 6 (Supplementary Figure S1A, right). The AP4 targets &lt;i&gt;MIR22 host gene&lt;/i&gt; (&lt;i&gt;MIR22HG&lt;/i&gt;) and &lt;i&gt;E-&lt;/i&gt;&lt;i&gt;cadherin 1&lt;/i&gt; (&lt;i&gt;CDH1&lt;/i&gt;) were down-regulated after MYC activation in &lt;i&gt;AP4&lt;/i&gt;-WT1 DLD-1/pRTR-&lt;i&gt;c-MYC&lt;/i&gt;-VSV cells (Supplementary Figure S1B). MAPK signaling effectors, including c-&lt;i&gt;Fos proto-oncogene&lt;/i&gt; (&lt;i&gt;FOS&lt;/i&gt;), c-&lt;i&gt;Jun proto-oncogene&lt;/i&gt; (&lt;i&gt;JUN&lt;/i&gt;) and &lt;i&gt;c-J&lt;/i&gt;&lt;i&gt;unB proto-oncogene&lt;/i&gt; (&lt;i&gt;JUNB&lt;/i&gt;), were over-represented in cluster 6. Additional MAPK signaling pathway components. such as &lt;i&gt;c-Jun N-terminal kinase 1&lt;/i&gt; (&lt;i&gt;JNK1&lt;/i&gt;), &lt;i&gt;mitogen-activated protein kinase kinase kinase 1&lt;/i&gt; (&lt;i&gt;MAP3K1&lt;/i&gt;), &lt;i&gt;mitogen-activated protein kinase kinase kinase 13&lt;/i&gt; (&lt;i&gt;MAP3K13&lt;/i&gt;), &lt;i&gt;mitogen-activated protein kinase kinase 3&lt;/i&gt; (&lt;i&gt;MAP2K3&lt;/i&gt;), &lt;i&gt;mitogen-activated protein kinase kinase 7&lt;/i&gt; (&lt;i&gt;MAP2K7&lt;/i&gt;) and &lt;i&gt;FOS&lt;/i&gt;-&lt;i&gt;like&lt;/i&gt; &lt;i&gt;1&lt;/i&gt; (&lt;i&gt;FOSL1&lt;/i&gt;) were found in clusters 3-5 (Supplementary Figure S1B). Interestingly, &lt;i&gt;MAP3K13, MAP2K7, JNK1&lt;/i&gt; and &lt;i&gt;FOSL1&lt;/i&gt; were induced by MYC in an &lt;i&gt;AP4&lt;/i&gt;-dependent manner (Supplementary Figure S1C-D).&lt;/p&gt;&lt;p&gt;Notably, &lt;i&gt;MAP3K13&lt;/i&gt;, &lt;i&gt;FOSL1, JNK1&lt;/i&gt; and &lt;i&gt;MAP2K7&lt;/i&gt; were also up-regulated after activating &lt;i&gt;AP4&lt;/i&gt; for 48 or 72 hours (Figure 1A) and showed AP4-binding sites (CAGCTG) and AP4 occupancy (Supplementary Figure S2A). Therefore, these genes presumably represent direct AP4 targets. MAP3K13 and FOSL1 protein and phosphorylated JNK1 were up-regulated after &lt;i&gt;AP4&lt;/i&gt; activation, whereas JNK1 protein levels remained unch","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 3","pages":"433-437"},"PeriodicalIF":16.2,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139472306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular metabolism: A key player in cancer ferroptosis","authors":"Xianjie Jiang,&nbsp;Qiu Peng,&nbsp;Mingjing Peng,&nbsp;Linda Oyang,&nbsp;Honghan Wang,&nbsp;Qiang Liu,&nbsp;Xuemeng Xu,&nbsp;Nayiyuan Wu,&nbsp;Shiming Tan,&nbsp;Wenjuan Yang,&nbsp;Yaqian Han,&nbsp;Jinguan Lin,&nbsp;Longzheng Xia,&nbsp;Yanyan Tang,&nbsp;Xia Luo,&nbsp;Jie Dai,&nbsp;Yujuan Zhou,&nbsp;Qianjin Liao","doi":"10.1002/cac2.12519","DOIUrl":"10.1002/cac2.12519","url":null,"abstract":"<p>Cellular metabolism is the fundamental process by which cells maintain growth and self-renewal. It produces energy, furnishes raw materials, and intermediates for biomolecule synthesis, and modulates enzyme activity to sustain normal cellular functions. Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions, including programmed cell death. Ferroptosis is a recently discovered form of iron-dependent programmed cell death. The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression. However, the role of cellular metabolism, particularly glucose and amino acid metabolism, in cancer ferroptosis is not well understood. Here, we reviewed glucose, lipid, amino acid, iron and selenium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process. Additionally, we provided a detailed overview of agents used to induce cancer ferroptosis. We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellular redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron-induced cell death, resulting in enhanced tumor cell killing. The combination of ferroptosis inducers and cellular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 2","pages":"185-204"},"PeriodicalIF":16.2,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139459766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023","authors":"Feng-Hua Wang,&nbsp;Xiao-Tian Zhang,&nbsp;Lei Tang,&nbsp;Qi Wu,&nbsp;Mu-Yan Cai,&nbsp;Yuan-Fang Li,&nbsp;Xiu-Juan Qu,&nbsp;Hong Qiu,&nbsp;Yu-Jing Zhang,&nbsp;Jie-Er Ying,&nbsp;Jun Zhang,&nbsp;Ling-Yu Sun,&nbsp;Rong-Bo Lin,&nbsp;Chang Wang,&nbsp;Hao Liu,&nbsp;Miao-Zhen Qiu,&nbsp;Wen-Long Guan,&nbsp;Sheng-Xiang Rao,&nbsp;Jia-Fu Ji,&nbsp;Yan Xin,&nbsp;Wei-Qi Sheng,&nbsp;Hui-Mian Xu,&nbsp;Zhi-Wei Zhou,&nbsp;Ai-Ping Zhou,&nbsp;Jing Jin,&nbsp;Xiang-Lin Yuan,&nbsp;Feng Bi,&nbsp;Tian-Shu Liu,&nbsp;Han Liang,&nbsp;Yan-Qiao Zhang,&nbsp;Guo-Xin Li,&nbsp;Jun Liang,&nbsp;Bao-Rui Liu,&nbsp;Lin Shen,&nbsp;Jin Li,&nbsp;Rui-Hua Xu","doi":"10.1002/cac2.12516","DOIUrl":"10.1002/cac2.12516","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti-angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)-positive and deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 1","pages":"127-172"},"PeriodicalIF":16.2,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12516","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139063385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of antibody-drug conjugates in cancer: Overview and prospects","authors":"Dan-Yun Ruan,&nbsp;Hao-Xiang Wu,&nbsp;Qi Meng,&nbsp;Rui-Hua Xu","doi":"10.1002/cac2.12517","DOIUrl":"10.1002/cac2.12517","url":null,"abstract":"<p>In recent years, remarkable breakthroughs have been reported on antibody-drug conjugates (ADCs), with 15 ADCs successfully entering the market over the past decade. This substantial development has positioned ADCs as one of the fastest-growing domains in the realm of anticancer drugs, demonstrating their efficacy in treating a wide array of malignancies. Nonetheless, there is still an unmet clinical need for wider application, better efficacy, and fewer side effects of ADCs. An ADC generally comprises an antibody, a linker and a payload, and the combination has profound effects on drug structure, pharmacokinetic profile and efficacy. Hence, optimization of the key components provides an opportunity to develop ADCs with higher potency and fewer side effects. In this review, we comprehensively reviewed the current development and the prospects of ADC, provided an analysis of marketed ADCs and the ongoing pipelines globally as well as in China, highlighted several ADC platforms and technologies specific to different pharmaceutical enterprises and biotech companies, and also discussed the new related technologies, possibility of next-generation ADCs and the directions of clinical research.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 1","pages":"3-22"},"PeriodicalIF":16.2,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12517","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139063437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NHE7 upregulation potentiates the uptake of small extracellular vesicles by enhancing maturation of macropinosomes in hepatocellular carcinoma","authors":"Yue Yao,&nbsp;Yi Xu,&nbsp;Liang Yu,&nbsp;Ting-Mao Xue,&nbsp;Zhi-Jie Xiao,&nbsp;Pui-Chi Tin,&nbsp;Hiu-Ling Fung,&nbsp;Hoi-Tang Ma,&nbsp;Jing-Ping Yun,&nbsp;Judy Wai Ping Yam","doi":"10.1002/cac2.12515","DOIUrl":"10.1002/cac2.12515","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Small extracellular vesicles (sEVs) mediate intercellular communication that contributes to hepatocellular carcinoma (HCC) progression via multifaceted pathways. The success of cell entry determines the effect of sEV on recipient cells. Here, we aimed to delineate the mechanisms underlying the uptake of sEV in HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Macropinocytosis was examined by the ability of cells to internalize dextran and sEV. Macropinocytosis was analyzed in Na(+)/H(+) exchanger 7 (<i>NHE7</i>)-knockdown and -overexpressing cells. The properties of cells were studied using functional assays. pH biosensor was used to evaluate the intracellular and endosomal pH. The expression of NHE7 in patients’ liver tissues was examined by immunofluorescent staining. Inducible silencing of NHE7 in established tumors was performed to reveal the therapeutic potential of targeting NHE7.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The data revealed that macropinocytosis controlled the internalization of sEVs and their oncogenic effect on recipient cells. It was found that metastatic HCC cells exhibited the highest efficiency of sEV uptake relative to normal liver cells and non-metastatic HCC cells. Attenuation of macropinocytic activity by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) limited the entry of sEVs and compromised cell aggressiveness. Mechanistically, we delineated that high level of NHE7, a sodium-hydrogen exchanger, alkalized intracellular pH and acidized endosomal pH, leading to the maturation of macropinosomes. Inducible inhibition of NHE7 in established tumors developed in mice delayed tumor development and suppressed lung metastasis. Clinically, NHE7 expression was upregulated and linked to dismal prognosis of HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study advances the understanding that NHE7 enhances sEV uptake by macropinocytosis to promote the malignant properties of HCC cells. Inhibition of sEV uptake via macropinocytosis can be exploited as a treatment alone or in combination with conventional therapeutic approaches for HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 2","pages":"251-272"},"PeriodicalIF":16.2,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}