Cancer Biology & Medicine最新文献

{"title":"Mechanisms underlying prostate cancer sensitivity to reactive oxygen species: overcoming radiotherapy resistance and recent clinical advances.","authors":"Meidan Wang, Rui Xing, Liqun Wang, Mingyue Pan, Ruoyun Zhang, Ting Li, Weiqiang Sun, Jing Zhou","doi":"10.20892/j.issn.2095-3941.2024.0584","DOIUrl":"10.20892/j.issn.2095-3941.2024.0584","url":null,"abstract":"<p><p>Prostate cancer (PCa) is a leading cause of cancer-related mortality among men. Radiotherapy is the cornerstone of PCa treatment. However, a major limitation of radiotherapy is the development of resistance, which compromises treatment efficacy. Reactive oxygen species (ROS), which are generated by radiation, have a dual role in PCa by inducing DNA damage and apoptosis, while also promoting tumor progression and radioresistance. Elevated ROS levels enhance metabolic reprogramming, activate oncogenic pathways, and influence the tumor microenvironment by modulating immune responses and promoting the epithelial-mesenchymal transition (EMT). Key molecular mechanisms, including the Nrf2/Keap1 signaling axis, Bcl-2 mutations, and Speckle-type POZ protein alterations, contribute to radioresistance by enhancing antioxidant defenses and DNA repair capacity. Additionally, the interplay between hypoxia, androgen receptor variants (AR-Vs), and ferroptosis regulators further influence radiotherapy outcomes. Understanding these resistance mechanisms is crucial for developing targeted strategies to enhance radiosensitivity and improve therapeutic outcomes in PCa patients.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607486","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":"Target identification of natural products in cancer with chemical proteomics and artificial intelligence approaches.","authors":"Guohua Li, Qian Shi, Qibiao Wu, Xinbing Sui","doi":"10.20892/j.issn.2095-3941.2025.0145","DOIUrl":"10.20892/j.issn.2095-3941.2025.0145","url":null,"abstract":"<p><p>Natural products (NPs) have long been recognized for their therapeutic potential, especially in cancer treatment, due to an ability to interact with multiple cellular pathways. The identification of molecular targets for NPs is a critical step in understanding anticancer mechanisms, with chemical proteomics emerging as a powerful approach. Both label-based and -free proteomic techniques have been utilized to identify these targets, each with their own advantages and limitations. While label-based methods provide high specificity through chemical tagging, the requirement for labeling can be a limitation, potentially altering NP natural properties. Conversely, label-free techniques allow for the detection of NP-protein interactions without structural modification but may struggle with transient interactions or low-abundance targets. Recent advances in artificial intelligence (AI) have further enhanced the field by improving target prediction and streamlining data analysis. AI-driven models, especially machine learning algorithms, have proven effective in processing complex proteomic data and predicting potential NP-protein interactions. The integration of AI with chemical proteomics accelerates target identification and deepens our understanding of the molecular mechanisms underlying the anticancer effects of NPs. This review explores the application of chemical proteomics and AI in the identification of cancer-related targets for NPs, highlighting current challenges and future directions for clinical translation.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":"22 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590550","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":"The polarity protein Par3 enhances renal cell carcinoma metastasis <i>via</i> YAP/TAZ activation.","authors":"Soo Lee, Jonathan Balcazar, Karla Davis, Rey-Chen Pong, Jer-Tsong Hsieh, Payal Kapur, Xiaosong Meng","doi":"10.20892/j.issn.2095-3941.2024.0297","DOIUrl":"10.20892/j.issn.2095-3941.2024.0297","url":null,"abstract":"<p><strong>Objective: </strong>Partitioning defective protein 3 (Par3) has recently been found to have important roles in cancer progression. Interestingly, Par3's functions vary among cancers: both Par3 elevation (in the prostate or liver) and loss (in the breast or lung) have been implicated in cancer metastasis. Although Par3 overexpression has been correlated with diminished survival in renal cell carcinoma (RCC), data indicating the role of Par3 in RCC metastasis are lacking. Given reports of interactions between Par3 and oncoproteins such as Yes-associated protein (YAP)/WW domain-containing transcription regulator 1 (TAZ), we investigated whether Par3-mediated RCC metastasis might be due to activation of the Hippo pathway components YAP and TAZ.</p><p><strong>Methods: </strong>Par3 levels were analyzed in RCC cell lines and human RCC patient tissues by western blotting and immunohistochemical (IHC) staining, as appropriate. Co-immunoprecipitation (co-IP) and immunofluorescence studies were conducted to examine the interaction between Par3 and YAP. Quantitative PCR and luciferase assays were used to investigate the effects of Par3 on YAP target gene expression and co-transcriptional regulation. PDZ domain deletion mutants of Par3 were generated to elucidate the structural basis of the interaction between Par3 and YAP.</p><p><strong>Results: </strong>Higher Par3 levels were found in distant-organ-RCC-metastasis-derived ACHN sublines than wild type ACHN cell lines. Par3 levels were also higher in the patient tissue obtained from metastatic sites than in normal kidney and primary RCC tumor tissues. Co-IP and IHC experiments demonstrated that Par3 directly interacted and co-localized with YAP/TAZ proteins. Moreover, Par3 upregulated the transcription of YAP/TAZ downstream target genes and increased the luciferase activity of YAP/TAZ responsive elements. PDZ domain 3 in the <i>PARD3</i> gene was demonstrated to be particularly important in the interactions between Par3 and YAP. Furthermore, Par3 was found to upregulate intracellular levels of YAP/TAZ molecules and promote nuclear translocation of YAP.</p><p><strong>Conclusions: </strong>Together, these results indicate the role of Par3 in RCC metastasis, <i>via</i> driving metastatic RCC progression by promoting the YAP/TAZ pathway.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583195","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":"Novel diagnostic and therapeutic strategies based on PANoptosis for hepatocellular carcinoma.","authors":"Jie Xiang, Yukai Li, Shengmin Mei, Zhiyan Ou, Li Wang, Yang Ke, Zhiwei Li","doi":"10.20892/j.issn.2095-3941.2025.0150","DOIUrl":"10.20892/j.issn.2095-3941.2025.0150","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC), a highly aggressive liver cancer, poses a large medical care burden worldwide. The prognosis of patients with HCC is poor, owing to recurrence and metastasis after common treatment methods. Therefore, identifying new targets to eliminate HCC cells is critical for treatment of HCC without recurrence. PANoptosis, a novel inflammatory cell death pathway, has become an intensively investigated area in recent years. The concept of PANoptosis has brought new hope for HCC therapy, given recent evidence implicating this form of programmed cell death in cancer progression, prognosis, and resistance to chemotherapy and immunotherapy. Despite increasing reviews describing the role of PANoptosis in various cancer types, to our knowledge, no systematic review has examined the implications of PANoptosis in HCC. Therefore, we sought to provide the first systematic review of the regulatory mechanisms and therapeutic potential of PANoptosis in HCC. We summarize recent progress in exploration of the role of PANoptosis in HCC, particularly regulation of the HCC tumor microenvironment by PANoptosis. Finally, we highlight the potential of PANoptosis-based diagnostic and therapeutic strategies for HCC.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583194","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":"Drugging the 'undruggable' KRAS: breakthroughs, challenges, and opportunities in pancreatic cancer.","authors":"Nawaz Khan, Umar Raza, Syed Aqib Ali Zaidi, Muhadaisi Nuer, Kayisaier Abudurousuli, Yipaerguli Paerhati, Alifeiye Aikebaier, Wenting Zhou","doi":"10.20892/j.issn.2095-3941.2025.0122","DOIUrl":"10.20892/j.issn.2095-3941.2025.0122","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis that is driven primarily by oncogenic KRAS mutations present in > 90% of cases. KRAS mutations, particularly the G12D mutation which dominates in PDAC, fuel tumor initiation, progression, and immune evasion, thereby contributing to therapy resistance. Nevertheless, KRAS has long been considered \"undruggable\" due to its structure. Recent advances have spurred transformative progress in direct KRAS inhibition. While FDA-approved mutation-specific and pan-KRAS inhibitors show limited efficacy in PDAC, emerging agents (MRTX1133 and RMC-9805) have demonstrated preclinical promise. However, resistance remains a critical hurdle and is driven by pathway reactivation, secondary mutations, and metabolic adaptations. Alternative strategies targeting upstream regulators (SHP2 and SOS1) aim to block KRAS activation and associated resistance mechanisms. Preclinical studies have also highlighted synergistic benefits of combining KRAS inhibitors with MEK, PI3K, or CDK4/6 inhibitors, which are now undergoing clinical evaluation. Immunotherapies, including KRAS-targeted vaccines and adoptive T-cell therapies, have further expanded the therapeutic landscape of enhancing KRAS-targeted therapies in PDAC. The molecular basis of KRAS-driven PDAC, current inhibitors, resistance mechanisms, and innovative strategies are discussed herein to address treatment barriers. Opportunities to improve clinical outcomes are underscored in this challenging malignancy by integrating insights from preclinical and clinical research.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583193","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":"High-precision immune-related plasma proteomics profiling predicts response to immunotherapy in patients with triple-negative breast cancer.","authors":"Yuling Xiao, Hang Zhang, Yi Xiao, Ying Wang, Jing Zhang, Qi Hua, Pengchen Hu, Xinyan Lyu, Weihua Shou, Xin Hu, Zhiming Shao, Yizhou Jiang, Wei Huang, Jinxiu Shi","doi":"10.20892/j.issn.2095-3941.2025.0038","DOIUrl":"10.20892/j.issn.2095-3941.2025.0038","url":null,"abstract":"<p><strong>Objective: </strong>While immunotherapy holds great potential for triple-negative breast cancer (TNBC), the lack of non-invasive biomarkers to identify beneficiaries limits the application.</p><p><strong>Methods: </strong>Paired baseline, on-treatment, and post-treatment plasma samples were collected from 195 TNBC patients receiving anti-PD-1 immunotherapy in this retrospective study conducted at the Fudan University Shanghai Cancer Center (FUSCC) for sequential high-precision proteomic profiling.</p><p><strong>Results: </strong>ARG1, NOS3, and CD28 were identified as plasma proteins significantly associated with the response to immunotherapy in neoadjuvant settings or in advanced stages of TNBC. Matched single-cell RNA sequencing data were incorporated to correlate peripheral plasma with the tumor microenvironment. Furthermore, the Plasma Immuno Prediction Score was developed to demonstrate significant predictive power for evaluating the efficacy and prognosis of patients undergoing neoadjuvant immunotherapy.</p><p><strong>Conclusions: </strong>The results underscore the importance of systemic immunity in the immunotherapy response and support the use of plasma protein profiles as a feasible tool for enhancing personalized management of immunotherapy in breast cancer.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559305","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":"Breast surgeons at the forefront: preserving lymph nodes for enhanced immunotherapy efficacy.","authors":"Zhiqiang Shi, Qiuchen Zhao, Yongsheng Wang, Pengfei Qiu","doi":"10.20892/j.issn.2095-3941.2025.0251","DOIUrl":"10.20892/j.issn.2095-3941.2025.0251","url":null,"abstract":"","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559304","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":"Neutrophils in cancer: from immune defense to tumor promotion.","authors":"Zhen Wang, Hanwen Hu, Yunjia Bao, Liwei Pang, Chenghui Yang","doi":"10.20892/j.issn.2095-3941.2025.0023","DOIUrl":"10.20892/j.issn.2095-3941.2025.0023","url":null,"abstract":"<p><p>Neutrophils are the protagonists of the host immune response, possessing potent antimicrobial and inflammatory capacities. The neutrophil reservoir as well as the development, mobilization, chemotaxis, pro-inflammatory activity, and clearance of neutrophils are strictly regulated to prevent inflammation-induced tissue damage. Inflammation pervades almost every type of cancer. However, there is growing awareness that although the tumor microenvironment has the capacity to recruit neutrophils, the functions are diverse and include roles other than that of sentinels in cancer. This review highlights the heterogeneity of neutrophils in tumors, discusses the dual role of neutrophils as angels and demons in tumorigenesis, invasion, and metastasis, and examines the potential of neutrophils as targets in clinical therapy.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552414","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":"PI3Kβ moonlights as a protein kinase: driving fatty acid metabolism and histone acetylation in cancer.","authors":"Yixin Duan, Juanjuan Liu, Jianxin Xu, Jing Fang","doi":"10.20892/j.issn.2095-3941.2025.0216","DOIUrl":"10.20892/j.issn.2095-3941.2025.0216","url":null,"abstract":"","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526550","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":"Beyond gold: the chemoenhancing mechanism and therapeutic potential of auranofin in melanoma.","authors":"Xiaofeng Wang, Yingnan Liu, Wuqiong Zhang, Zhongda Li, Su Li, Jiaxin Chen, Qi Li, Xiaoman Suo, Yanqiao Zeng, Guofang Zhang, Yang Li","doi":"10.20892/j.issn.2095-3941.2025.0026","DOIUrl":"10.20892/j.issn.2095-3941.2025.0026","url":null,"abstract":"<p><strong>Objective: </strong>The objective of the current study was to evaluate the chemosensitizing capacity of auranofin (AF), a gold (I) complex traditionally used in rheumatoid arthritis treatment, in potentiating the cytotoxic effects of doxorubicin (DOX) in melanoma cell models, specifically drug-sensitive (B16F10) and multidrug-resistant (B16F10/ADR) variants.</p><p><strong>Methods: </strong>Experimental measurements, including <i>in vitro</i> cytotoxicity and apoptosis assays, surface plasmon resonance (SPR), immunoblotting assays, as well as theoretical calculations, such as molecular docking and molecular dynamics (MD) simulations, were used to systematically delineate the interaction dynamics between AF and thioredoxin reductase 1 (TrxR1). The anti-tumor efficacy of co-treatment with AF and DOX was assessed by examining cell viability and apoptotic rates.</p><p><strong>Results: </strong>Co-treatment with AF and DOX significantly increased anti-tumor efficacy, as evidenced by reduced cell viability and increased apoptotic rates. This synergistic effect was attributed to inhibition of TrxR1 by AF, which compromised tumor cell antioxidant defenses and elevated intracellular reactive oxygen species (ROS), thereby enhancing apoptotic pathways. Notably, AF treatment mitigated the heightened TrxR activity in DOX-resistant cells, intensifying the pro-oxidant effects of DOX, leading to increased ROS production and cell death. The data also showed that AF binds with high affinity to the selenocysteine residue within the catalytic site of TrxR1, which partially overlapped with the binding site of the endogenous substrate, thioredoxin (Trx), but with greater avidity. This unique binding configuration impedes the reduction of Trx by TrxR1, triggering an apoptotic response in cancer cells.</p><p><strong>Conclusions: </strong>This study underscores the chemosensitizing potential of AF in overcoming multidrug resistance in cancer therapy through redox modulation. The molecular mechanism of action underlying AF on TrxR1 demonstrated the unique binding configuration that impedes the reduction of Trx by TrxR1 and instigates an apoptotic response in cancer cells. These findings pave the way for the clinical application of AF as a chemosensitizer, offering a novel approach to augment the efficacy of existing chemotherapy regimens.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526548","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}