{"title":"An open-label, single-arm, multicenter, phase II trial of bireociclib as monotherapy for heavily pretreated HR-positive, HER2-negative advanced breast cancer patients: BRIGHT-1 trial.","authors":"Jiayu Wang, Qingyuan Zhang, Tao Sun, Huiping Li, Ying Cheng, Zhongsheng Tong, Huihui Li, Wei Li, Jingfen Wang, Yuee Teng, Xinhong Wu, Jing Cheng, Zhendong Chen, Zhengqiu Zhu, Li Wang, Mingming Liu, Xianghui Duan, Lingmei Xu, Binghe Xu","doi":"10.1002/cac2.70009","DOIUrl":"https://doi.org/10.1002/cac2.70009","url":null,"abstract":"<p><strong>Background: </strong>Bireociclib (XZP-3287) is a novel selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor, with a favorable safety profile demonstrated in preclinical and phase I studies. BRIGHT-1 aimed to further explore the efficacy and safety of bireociclib monotherapy in patients with locally advanced, recurrent or metastatic, hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR<sup>+</sup>/HER2<sup>-</sup>) breast cancer who had progressed on or after prior chemotherapy and endocrine therapy in advanced settings, without previous exposure to CDK4/6 inhibitors.</p><p><strong>Methods: </strong>In this open-label phase II trial, eligible patients received bireociclib 480 mg twice daily (BID) until disease progression or intolerable toxicities. The primary endpoint was the confirmed objective response rate (ORR) assessed by an independent review committee (IRC). The secondary endpoints included progression-free survival (PFS), investigator-assessed ORR, disease control rate (DCR), clinical benefit rate (CBR), duration of response (DoR), overall survival (OS), safety and the pharmacokinetic properties of bireociclib.</p><p><strong>Results: </strong>A total of 131 patients were enrolled. At data cutoff (July 31, 2023), the IRC-assessed ORR was 29.8% (95% confidence interval [CI], 22.1% to 38.4%), with a DCR of 73.3% (95% CI, 64.8% to 80.6%), CBR of 42.0% (95% CI, 33.4% to 50.9%) and a median DoR of 15.2 months (95% CI, 9.5 months to not reached). The median PFS was 11.0 months (95% CI, 7.3 months to 12.9 months) assessed by the IRC, and the median OS was 29.0 months (95% CI, 24.9 months to not reached). The most frequently reported treatment-emergent adverse events (TEAEs) of any grade were diarrhea (93.1%), neutrophil count decreased (87.0%), white blood cell decreased (86.3%), vomiting (78.6%), anemia (72.5%), and platelet count decreased (72.5%). The grade ≥3 TEAEs occurred in 109 (83.2%) patients. The most common grade ≥3 TEAEs were neutrophil count decreased (43.5%), white blood cell decreased (32.8%), hypokalemia (20.6%), and diarrhea (19.1%).</p><p><strong>Conclusions: </strong>Bireociclib monotherapy at 480 mg BID exhibited promising and sustained clinical activity, with no unexpected and acceptable toxicity in patients with recurrent or metastatic HR<sup>+</sup>/HER2<sup>-</sup> breast cancer who had progressed on or after previous therapy.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov ID, NCT04539496.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514744","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}
{"title":"Neoadjuvant chemotherapy plus anlotinib in the treatment of resectable head and neck squamous cell carcinoma: A pilot phase II trial.","authors":"Qianting He, Shuojin Huang, Dongxiao Tang, Congyuan Cao, Wanhang Zhou, Rongsong Ling, Jie Chen, Bokai Yun, Xin Zheng, Yanchen Li, Anxun Wang, Demeng Chen","doi":"10.1002/cac2.70006","DOIUrl":"https://doi.org/10.1002/cac2.70006","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457004","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}
{"title":"Helicobacter pylori CagA elevates FTO to induce gastric cancer progression via a \"hit-and-run\" paradigm.","authors":"Bing He, Yiyang Hu, Yuyun Wu, Chao Wang, Limin Gao, Chunli Gong, Zhibin Li, Nannan Gao, Huan Yang, Yufeng Xiao, Shiming Yang","doi":"10.1002/cac2.70004","DOIUrl":"https://doi.org/10.1002/cac2.70004","url":null,"abstract":"<p><strong>Background: </strong>Helicobacter pylori (H. pylori) infection contributes significantly to gastric cancer (GC) progression. The intrinsic mechanisms of H. pylori-host interactions and their role in promoting GC progression need further investigation. In this study, we explored the potential role of fat mass and obesity-associated protein (FTO) in mediating Cytotoxin-associated gene A (CagA)-induced GC progression.</p><p><strong>Methods: </strong>The effects of H. pylori infection on N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification were evaluated in both human samples and GC cell lines. The function of FTO in the progression of GC was elucidated through in vitro and in vivo studies. A series of techniques, including methylated RNA immunoprecipitation sequencing, RNA sequencing, RNA binding protein immunoprecipitation, and chromatin immunoprecipitation assays, were utilized to investigate the mechanism by which FTO mediates the capacity of cagA-positive H. pylori to promote GC progression. Furthermore, the therapeutic potential of the FTO inhibitor meclofenamic acid (MA) in impeding GC progression was evaluated across GC cells, animal models, and human GC organoids.</p><p><strong>Results: </strong>Infection with cagA-positive H. pylori upregulated the expression of FTO, which was essential for CagA-mediated GC metastasis and significantly associated with a poor prognosis in GC patients. Mechanistically, CagA delivered by H. pylori enhanced FTO transcription via Jun proto-oncogene. Elevated FTO induced demethylation of m<sup>6</sup>A and inhibited the degradation of heparin-binding EGF-like growth factor (HBEGF), thereby facilitating the epithelial-mesenchymal transition (EMT) process in GC cells. Interestingly, eradication of H. pylori did not fully reverse the increases in FTO and HBEGF levels induced by cagA-positive H. pylori. However, treatment with a combination of antibiotics and MA substantially inhibited cagA-positive H. pylori-induced EMT and prevented GC metastasis.</p><p><strong>Conclusion: </strong>Our study revealed that FTO mediates the \"hit-and-run\" mechanism of CagA-induced GC progression, which suggests that the therapeutic targeting of FTO could offer a promising approach to the prevention of CagA-induced cancer progression.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440296","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}
Dan Shan, Jinling Song, Yuqing Ren, Yuyuan Zhang, Yuhao Ba, Peng Luo, Quan Cheng, Hui Xu, Siyuan Weng, Anning Zuo, Shutong Liu, Xinwei Han, Jinhai Deng, Zaoqu Liu
{"title":"Copper in cancer: friend or foe? Metabolism, dysregulation, and therapeutic opportunities.","authors":"Dan Shan, Jinling Song, Yuqing Ren, Yuyuan Zhang, Yuhao Ba, Peng Luo, Quan Cheng, Hui Xu, Siyuan Weng, Anning Zuo, Shutong Liu, Xinwei Han, Jinhai Deng, Zaoqu Liu","doi":"10.1002/cac2.70005","DOIUrl":"https://doi.org/10.1002/cac2.70005","url":null,"abstract":"<p><p>Copper, one of the essential nutrients for the human body, acts as an electron relay in multiple pathways due to its redox properties. Both deficiencies and excesses of copper lead to cellular fragility. Therefore, it can manifest pro- and anti-cancer properties in tumors. Therefore, it is crucial to clarify the copper activity within the cell. We have thoughtfully summarized the metabolic activities of copper from a macro and micro perspective. Cuproptosis, as well as other forms of cell death, is directly or indirectly interfered with by Cu<sup>2+</sup>, causing cancer cell death. Meanwhile, we did pan-cancer analysis of cuproptosis-related genes to further clarify the roles of these genes. In addition, copper has been found to be involved in multiple pathways within the metastasis of cancer cells. Given the complexity of copper's role, we are compelled to ask: is copper a friend or a foe? Up to now, copper has been used in various clinical applications, including protocols for measurement of copper concentration and bioimaging of radioactive <sup>64</sup>Cu. But therapeutically it is still a continuation of the old medicine, and new possibilities need to be explored, such as the use of nanomaterials. Some studies have also shown that copper has considerable interventional power in metabolic cancers, which provides the great applications potential of copper therapy in specific cancer types. This paper reviews the dual roles played by cuproptosis in cancer from the new perspectives of oxidative stress, cell death, and tumor metastasis, and points out the value of its application in specific cancer types, summarizes the value of its testing and imaging from the perspective of clinical application as well as the current feasible options for the new use of the old drugs, and emphasizes the prospects for the application of nano-copper.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405754","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}
Mohammad Mahmoudi Gomari, Taha Ghantabpour, Nima Pourgholam, Neda Rostami, Stephen M Hatfield, Farzaneh Namazifar, Shadi Abkhiz, Seyed Sadegh Eslami, Mahsa Ramezanpour, Mahsa Darestanifarahani, Igor Astsaturov, Sidi A Bencherif
{"title":"Breaking barriers: Smart vaccine platforms for cancer immunomodulation.","authors":"Mohammad Mahmoudi Gomari, Taha Ghantabpour, Nima Pourgholam, Neda Rostami, Stephen M Hatfield, Farzaneh Namazifar, Shadi Abkhiz, Seyed Sadegh Eslami, Mahsa Ramezanpour, Mahsa Darestanifarahani, Igor Astsaturov, Sidi A Bencherif","doi":"10.1002/cac2.70002","DOIUrl":"https://doi.org/10.1002/cac2.70002","url":null,"abstract":"<p><p>Despite significant advancements in cancer treatment, current therapies often fail to completely eradicate malignant cells. This shortfall underscores the urgent need to explore alternative approaches such as cancer vaccines. Leveraging the immune system's natural ability to target and kill cancer cells holds great therapeutic potential. However, the development of cancer vaccines is hindered by several challenges, including low stability, inadequate immune response activation, and the immunosuppressive tumor microenvironment, which limit their efficacy. Recent progress in various fields, such as click chemistry, nanotechnology, exosome engineering, and neoantigen design, offer innovative solutions to these challenges. These achievements have led to the emergence of smart vaccine platforms (SVPs), which integrate protective carriers for messenger ribonucleic acid (mRNA) with functionalization strategies to optimize targeted delivery. Click chemistry further enhances SVP performance by improving the encapsulation of mRNA antigens and facilitating their precise delivery to target cells. This review highlights the latest developments in SVP technologies for cancer therapy, exploring both their opportunities and challenges in advancing these transformative approaches.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122299","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}
{"title":"Evaluation of cervical cancer screening strategies in women living with HIV in Thailand.","authors":"Patumrat Sripan, Myrtille Prouté, Nicole Ngo-Giang-Huong, Samreung Rangdaeng, Chaiwat Putiyanun, Guttiga Halue, Prattana Leenasirimakul, Suchart Thongpaen, Sudanee Buranabanjasatean, Sophie Le Coeur, Tristan Delory","doi":"10.1002/cac2.70000","DOIUrl":"https://doi.org/10.1002/cac2.70000","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058278","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}
{"title":"Cuproplasia and cuproptosis, two sides of the coin.","authors":"Kaizhong Lu, Chandra Sugiarto Wijaya, Qinghua Yao, Hongchuan Jin, Lifeng Feng","doi":"10.1002/cac2.70001","DOIUrl":"https://doi.org/10.1002/cac2.70001","url":null,"abstract":"<p><p>Copper is an essential micronutrient in the human body, mainly acting as a crucial cofactor required for a wide range of physiological processes across nearly all cell types. Recent advances revealed that tumor cells seize copper to fulfill their rapid proliferation, metastasis, immune evasion, and so on by reprogramming the copper regulatory network, defined as cuproplasia. Thus, targeting copper chelation to reduce copper levels has been considered a rational tumor therapy strategy. However, overloaded copper ions could be toxic, which leads to the aggregation of lipoylated mitochondrial proteins and the depletion of iron-sulfur clusters, ultimately resulting in cell death, termed cuproptosis. Upon its discovery, cuproptosis has attracted great interest from oncologists, and targeting cuproptosis by copper ionophores exhibits as a potential anti-tumor therapy. In this review, we present the underlying mechanisms involved in cuproplasia and cuproptosis. Additionally, we sum up the chemicals targeting either cuproplasia or cuproptosis for cancer therapy. Further attention should be paid to distinguishing cancer patients who are suitable for targeting cuproplasia or cuproptosis.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045226","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}
{"title":"Cover Image, Volume 45, Issue 1","authors":"Jiali Yao, Linlin Ji, Guang Wang, Jin Ding","doi":"10.1002/cac2.12551","DOIUrl":"https://doi.org/10.1002/cac2.12551","url":null,"abstract":"<p>The cover image is based on the article <i>Effect of neutrophils on tumor immunity and immunotherapy resistance with underlying mechanisms</i> by Jiali Yao et al., https://doi.org/10.1002/cac2.12613.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12551","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143118821","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}