Muhammad Haris Sultan, Qi Zhan, Hao Jin, Xiaoyuan Jia, Yigang Wang
{"title":"Epigenetic modulation by oncolytic viruses: Implications for cancer therapeutic efficacy","authors":"Muhammad Haris Sultan, Qi Zhan, Hao Jin, Xiaoyuan Jia, Yigang Wang","doi":"10.1016/j.bbcan.2025.189270","DOIUrl":"10.1016/j.bbcan.2025.189270","url":null,"abstract":"<div><div>Among various therapeutic agents, Oncolytic Viruses (OVs) are the most promising anticancer therapeutics because of their tumor-specific targeting and capability to mediate an antitumor immune response. In this review, we will discuss how epigenetic reprogramming of both the host and tumor can facilitate increased sensitivity of tumors to OV therapy. OVs infect tumor cells and modulate epigenetic landscapes, including DNA methylation, histone modifications, and chromatin remodeling, as well as non-coding RNA expression that consequently induces immune responses. These epigenetic changes, including hypermethylation of tumor-associated antigen genes and chromatin accessibility alterations, enhance the immunogenicity of tumors to facilitate recognition by the immune system. Here, we provide a general review addressing this question by discussing the potential benefits of combining OVs with epigenetic drugs to combat resistance and promote treatment efficacy. This information illustrates the importance of personalized OV therapy regarding epigenome in individual profiles and transitions. Still, it extends difficulty in inducing with acquisitions of viral-induced changes globally and making translatable steps by creating cancer-specific predictive treatment models.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 2","pages":"Article 189270"},"PeriodicalIF":9.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043497","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}
Abdelrahman M. Elsayed , Muaiad Kittaneh , Colleen M. Cebulla , Mohamed H. Abdel-Rahman
{"title":"An overview of BAP1 biological functions and current therapeutics","authors":"Abdelrahman M. Elsayed , Muaiad Kittaneh , Colleen M. Cebulla , Mohamed H. Abdel-Rahman","doi":"10.1016/j.bbcan.2025.189267","DOIUrl":"10.1016/j.bbcan.2025.189267","url":null,"abstract":"<div><div><em>BRCA1-associated protein 1</em> (<em>BAP1</em>) is a tumor suppressor gene that was first identified in 1998. Germline loss-of-function variants in <em>BAP1</em> are associated with a tumor predisposition syndrome with at least four cancers: uveal melanoma (UM), malignant mesothelioma (MMe), renal cell carcinoma (RCC), and cutaneous melanoma (CM). Furthermore, somatic <em>BAP1</em> mutations are important drivers for several cancers most notably UM, MMe, RCC, intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). Emerging evidence substantiates the fundamental role of BAP1 in suppressing cancer initiation and progression by tuning DNA damage repair, apoptosis, ferroptosis, immune response, Warburg phenomenon, and metastasis. Multiple treatment strategies such as poly (ADP-ribose) polymerase (PARP) inhibitors, EZH2 inhibitors, alkylating agents, and immunotherapy have been used as potential therapies for <em>BAP1</em>-mutated tumors. Although these agents showed promising results in <em>BAP1</em>-mutated tumors in preclinical studies, the results of most clinical trials are still dismal. The objectives of this review are to summarize the current state of knowledge regarding the biological functions of BAP1, the implications of these functions in tumorigenesis, and the current progress in BAP1-targeted therapy.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 2","pages":"Article 189267"},"PeriodicalIF":9.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026146","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}
Patrycja Przygodzka , Izabela Szulc-Kielbik , Michal Kielbik , Marcin Pacholczyk , Magdalena Klink
{"title":"Neuromedin U in the tumor microenvironment - Possible actions in tumor progression","authors":"Patrycja Przygodzka , Izabela Szulc-Kielbik , Michal Kielbik , Marcin Pacholczyk , Magdalena Klink","doi":"10.1016/j.bbcan.2025.189269","DOIUrl":"10.1016/j.bbcan.2025.189269","url":null,"abstract":"<div><div>Tumor microenvironment (TME) has become a major focus of cancer research as a promising therapeutic target. TME comprises cancer cells surrounded by nonmalignant cells, vessels, lymphoid organs, immune cells, nerves, intercellular components, molecules and metabolites located within or near the tumor lesion.</div><div>Neuromedin U (NMU), a secretory peptide identified in the TME, has gained much attention as an important player in cancer and nonmalignant cell crosstalk. NMU receptors were detected in cancer cells as well as in nonmalignant TME components, such as immune, stromal and endothelial cells.</div><div>We propose here to discuss the concept that NMU secreted by cancer cells activates cellular components of TME and thus contributes to the formation of microenvironment that favors tumor growth and cancer progression. We summarized the available data on cancer tissues and cell types that have been identified as a source of NMU and/or receptor-expressing NMU targets. We made a critical selection of NMU-receptor positive cell types that are known components of the TME of most malignant tumors. Finally, we discussed whether NMUs and NMU receptors represent a potential therapeutic target for cancer treatment, and summarized information on the tools available to modulate their activity.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 2","pages":"Article 189269"},"PeriodicalIF":9.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026148","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}
Wenting Li , Nanshu Liu , Mingwei Chen , Dongjuan Liu , Sai Liu
{"title":"Metformin as an immunomodulatory agent in enhancing head and neck squamous cell carcinoma therapies","authors":"Wenting Li , Nanshu Liu , Mingwei Chen , Dongjuan Liu , Sai Liu","doi":"10.1016/j.bbcan.2025.189262","DOIUrl":"10.1016/j.bbcan.2025.189262","url":null,"abstract":"<div><div>Head and neck squamous cell carcinoma (HNSCC) remains a significant clinical challenge due to its aggressive behavior and poor prognosis, making the development of novel therapeutics with enhanced efficacy and minimal side effects critical. Metformin, a widely used antidiabetic agent, has recently emerged as a potential adjunctive therapy for HNSCC, exhibiting both direct anti-tumor and immunomodulatory effects. This review comprehensively explores the multifaceted role of metformin in shaping the tumor immune microenvironment within HNSCC. We emphasize its pivotal role in modulating immune cell populations and its potential for synergistic action with immunotherapeutic strategies. Furthermore, we address the current challenges associated with optimizing dosing regimens, identifying predictive biomarkers, and integrating metformin with immunotherapy. By dissecting these aspects, this review aims to pave the way for the development of personalized HNSCC treatment strategies that fully exploit the therapeutic potential of metformin.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 2","pages":"Article 189262"},"PeriodicalIF":9.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018177","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}
Liu Yang , Xingyue Wang , Shurong Wang , Jing Shen , Yaling Li , Shengli Wan , Zhangang Xiao , Zhigui Wu
{"title":"Targeting lipid metabolism in regulatory T cells for enhancing cancer immunotherapy","authors":"Liu Yang , Xingyue Wang , Shurong Wang , Jing Shen , Yaling Li , Shengli Wan , Zhangang Xiao , Zhigui Wu","doi":"10.1016/j.bbcan.2025.189259","DOIUrl":"10.1016/j.bbcan.2025.189259","url":null,"abstract":"<div><div>As immunosuppressive cells, Regulatory T cells (Tregs) exert their influence on tumor immune escape within the tumor microenvironment (TME) by effectively suppressing the activity of other immune cells, thereby significantly impeding the anti-tumor immune response. In recent years, the metabolic characteristics of Tregs have become a focus of research, especially the important role of lipid metabolism in maintaining the function of Tregs. Consequently, targeted interventions aimed at modulating lipid metabolism in Tregs have been recognized as an innovative and promising approach to enhance the effectiveness of tumor immunotherapy. This review presents a comprehensive overview of the pivotal role of lipid metabolism in regulating the function of Tregs, with a specific focus on targeting Tregs lipid metabolism as an innovative approach to augment anti-tumor immune responses. Furthermore, we discuss potential opportunities and challenges associated with this strategy, aiming to provide novel insights for enhancing the efficacy of cancer immunotherapy.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 2","pages":"Article 189259"},"PeriodicalIF":9.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973794","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}
Siuli Shaw (Conceptualization, Writing-original draft, drawing illustrations; reviewing and editing manuscript) , Subrata Kumar Pore (Draw diagram, Writing- reviewing & editing of manuscript) , Dutong Liu (Partially writing original-draft) , Tushar Kumeria (Reviewing and editing the manuscript) , Ranu Nayak (Conceptualization, Writing- editing and reviewing, Supervision) , Sudeep Bose (Conceptualization, Writing- editing and reviewing, Supervision)
{"title":"Combating chemoresistance: Current approaches & nanocarrier mediated targeted delivery","authors":"Siuli Shaw (Conceptualization, Writing-original draft, drawing illustrations; reviewing and editing manuscript) , Subrata Kumar Pore (Draw diagram, Writing- reviewing & editing of manuscript) , Dutong Liu (Partially writing original-draft) , Tushar Kumeria (Reviewing and editing the manuscript) , Ranu Nayak (Conceptualization, Writing- editing and reviewing, Supervision) , Sudeep Bose (Conceptualization, Writing- editing and reviewing, Supervision)","doi":"10.1016/j.bbcan.2025.189261","DOIUrl":"10.1016/j.bbcan.2025.189261","url":null,"abstract":"<div><div>Chemoresistance, a significant challenge in effective cancer treatment needs clear elucidation of the underlying molecular mechanism for the development of novel therapeutic strategies. Alterations in transporter pumps, oncogenes, tumour suppressor genes, mitochondrial function, DNA repair processes, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, epigenetic modifications, and exosome secretion lead to chemoresistance. Despite notable advancements in targeted cancer therapies employing both small molecules and macromolecules success rates remain suboptimal due to adverse effects like drug efflux, target mutation, increased mortality of normal cells, defective apoptosis, etc. This review proposes an advanced nanotechnological technique precisely targeting molecular determinants of chemoresistance which holds promise for enhancing cancer treatment efficacy. Further, the review explores various cancer hallmarks and pathways implicated in chemoresistance, current therapeutic modalities, and their limitations. It advocates the combination of nanoparticle-conjugated conventional drugs and natural compounds to specifically target molecular pathways that can potentially reverse or minimize chemoresistance incidences in cancer patients.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 2","pages":"Article 189261"},"PeriodicalIF":9.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973789","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":"Decoding the role of FOXP3 in esophageal cancer: Underlying mechanisms and therapeutic implications","authors":"Yuanyuan Wang, Lei Xue","doi":"10.1016/j.bbcan.2024.189211","DOIUrl":"10.1016/j.bbcan.2024.189211","url":null,"abstract":"<div><div>Esophageal cancer is a significant contributor to cancer-related mortality, and its poor prognosis is primarily attributed to the aggressive nature of the tumor and challenges in early detection. Currently, there are no ideal drugs developed for treatment, making it crucial to explore potential biomarkers and molecular targets for esophageal cancer. FOXP3, as a transcription factor and major regulator of regulatory T cells, not only plays a role in promoting or inhibiting tumor development in various types of cancer cells including esophageal cancer cells but also influences the function of Treg cells by regulating the expression of multiple genes. This paper provides an in-depth discussion on the functional properties, regulatory mechanisms, key signaling pathways, as well as the role and potential application of FOXP3 in treating esophageal cancer. Furthermore, it comprehensively analyzes the complex role of this transcription factor within the tumor immune microenvironment with an aim to aid in developing new potential targets for esophageal cancer treatment.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189211"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634326","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}
Hongjuan Yao , Liaoxin Luo , Rui Li , Yelin Zhao , Li Zhang , Milica Pešić , Lin Cai , Liang Li
{"title":"New insight into the role of SMAD4 mutation/deficiency in the prognosis and therapeutic resistance of pancreatic ductal adenocarcinomas","authors":"Hongjuan Yao , Liaoxin Luo , Rui Li , Yelin Zhao , Li Zhang , Milica Pešić , Lin Cai , Liang Li","doi":"10.1016/j.bbcan.2024.189220","DOIUrl":"10.1016/j.bbcan.2024.189220","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) patients have an unfavorable prognosis and disappointing treatment outcomes because of late diagnosis, high chemotherapy resistance, ineffective adjuvant chemotherapy, unavailable molecular targeted therapy, and profound immunosuppressive effects in the tumor microenvironment (TME). There are a variety of critical driver proteins, such as KRAS, TP53, PTEN and SMAD4, putatively involved in PDAC etiology. Current knowledge of their molecular mechanisms is still limited. <em>SMAD4</em> gene alterations in ∼55 % of patients emphasize its key role in PDAC progression, metastasis, resistance and immunity. Despite extensive studies on the TGF-β/SMAD pathway, the impact of SMAD4 mutation/deficiency on PDAC prognosis and treatment, especially its mechanism in drug resistance, has not yet been elucidated. This review summarizes the latest advances in the effect of SMAD4 deficiency on the prognosis and therapeutic resistance of PDAC patients. It might be a predictive and prognostic biomarker or therapeutic target to achieve the desired clinical benefits. Moreover, we discuss potential strategies to implement targeted therapies in terms of SMAD4 genetic status.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189220"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689901","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}
Dandan Shi , Jiejing Tao , Shuli Man , Ning Zhang , Long Ma , Lanping Guo , Luqi Huang , Wenyuan Gao
{"title":"Structure, function, signaling pathways and clinical therapeutics: The translational potential of STAT3 as a target for cancer therapy","authors":"Dandan Shi , Jiejing Tao , Shuli Man , Ning Zhang , Long Ma , Lanping Guo , Luqi Huang , Wenyuan Gao","doi":"10.1016/j.bbcan.2024.189207","DOIUrl":"10.1016/j.bbcan.2024.189207","url":null,"abstract":"<div><div>Cancer remains one of the most difficult human diseases to overcome because of its complexity and diversity. Signal transducers and transcriptional activators 3 (STAT3) protein has been found to be overexpressed in a wide range of cancer types. Hyperactivation of STAT3 is particularly associated with low survival in cancer patients. This review summarizes the specific molecular mechanisms of STAT3 in cancer development. STAT3 is activated by extracellular signals in the cytoplasm, interacts with different enzymes in the nucleus, mitochondria or endoplasmic reticulum, and subsequently participates in cancer development. The phosphorylated STAT3 at tyrosine 705 site (YP-STAT3) enters the nucleus and regulates a number of tumor-related biological processes such as angiogenesis, migration invasion, cell proliferation and cancer cell stemness. In contrast, the phosphorylated STAT3 at serine 727 site (SP-STAT3) is found on the mitochondria, affects electron respiration transport chain activity and thereby prevents tumor cell apoptosis. SP-STAT3 also appears on the mitochondria-associated endoplasmic reticulum membrane, influences the flow of Ca<sup>2+</sup>, and affects tumor progression. In addition, we summarize the direct and indirect inhibitors of STAT3 which are currently undergoing clinical studies. Some of them such as TTI101 and BBI608 have been approved by the FDA for the treatment of certain cancers. All in all, STAT3 plays an important role in cancer progression and becomes a potential target for cancer treatment.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189207"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585121","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}
Moyed Alsaadawe , Bakeel A. Radman , Jingyi Long , Mohenned Alsaadawi , Weiyi Fang , Xiaoming Lyu
{"title":"Epstein Barr virus: A cellular hijacker in cancer","authors":"Moyed Alsaadawe , Bakeel A. Radman , Jingyi Long , Mohenned Alsaadawi , Weiyi Fang , Xiaoming Lyu","doi":"10.1016/j.bbcan.2024.189218","DOIUrl":"10.1016/j.bbcan.2024.189218","url":null,"abstract":"<div><div>Numerous studies have demonstrated the importance of the Epstein-Barr Virus (EBV), which was initially identified in 1964 while studying Burkitt's lymphoma, in the development of a number of cancers, including nasopharyngeal carcinoma, Hodgkin's lymphoma, Burkitt's lymphoma, and EBV-associated gastric carcinoma. Gammaherpesvirus EBV is extremely common; by adulthood, over 90 % of people worldwide have been infected. Usually, the virus causes a permanent latent infection in B cells, epithelial cells, and NK/T cells. It then contributes to oncogenesis by inhibiting apoptosis and promoting unchecked cell proliferation through its latent proteins, which include EBNA-1, LMP1, and LMP2A. Tumor progression further accelerated by EBV's capacity to transition between latent and lytic phases, especially in cases of nasopharyngeal carcinoma. Although our understanding of the molecular underpinnings of EBV has advanced, there are still difficulties in identifying latent infections and creating targeted therapeutics. To tackle EBV-associated malignancies, current research efforts are concentrated on developing vaccines, developing better diagnostic tools, and developing targeted treatments. In order to improve treatment approaches and lower the incidence of EBV-related cancers worldwide, more research into the relationship between EBV and immune evasion and cancer formation is necessary.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189218"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645301","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}