Biochimica et biophysica acta. Reviews on cancer最新文献

{"title":"The crosstalk within tumor microenvironment and exosomes in pancreatic cancer","authors":"Michael Ochieng' Otieno ,&nbsp;Tomasz Powrózek ,&nbsp;Jesus Garcia-Foncillas ,&nbsp;Javier Martinez-Useros","doi":"10.1016/j.bbcan.2025.189308","DOIUrl":"10.1016/j.bbcan.2025.189308","url":null,"abstract":"<div><div>Pancreatic cancer is one of the most malignant tumors with a grim prognosis. Patients develop chemoresistance that drastically decreases their survival. The chemoresistance is mainly attributed to deficient vascularization of the tumor, intratumoral heterogeneity and pathophysiological barrier due to the highly desmoplastic tumor microenvironment. The interactions of cells that constitute the tumor microenvironment change its architecture into a cancer-permissive environment and stimulate cancer development, metastasis and treatment response. The cell-cell communication in the tumor microenvironment is often mediated by exosomes that harbour a diverse repertoire of molecular cargo, such as proteins, lipids, and nucleic acid, including messenger RNAs, non-coding RNAs and DNA. Therefore, exosomes can serve as potential targets as biomarkers and improve the clinical management of pancreatic cancer to overcome chemoresistance. This review critically elucidates the role of exosomes in cell-cell communication within the tumor microenvironment and how these interactions can orchestrate chemoresistance.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 3","pages":"Article 189308"},"PeriodicalIF":9.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776914","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":"The epipliancy journey: Tumor initiation at the mercy of identity crisis and epigenetic drift","authors":"Rahma Benhassoun ,&nbsp;Anne-Pierre Morel ,&nbsp;Victoria Jacquot ,&nbsp;Alain Puisieux ,&nbsp;Maria Ouzounova","doi":"10.1016/j.bbcan.2025.189307","DOIUrl":"10.1016/j.bbcan.2025.189307","url":null,"abstract":"<div><div>Cellular pliancy refers to the unique disposition of different stages of cellular differentiation to transform when exposed to specific oncogenic insults. This concept highlights a strong interconnection between cellular identity and tumorigenesis, and implies overcoming of epigenetic barriers defining cellular states. Emerging evidence suggests that the cell-type-specific response to intrinsic and extrinsic stresses is modulated by accessibility to certain areas of the genome. Understanding the interplay between epigenetic mechanisms, cellular differentiation, and oncogenic insults is crucial for deciphering the complex nature of tumorigenesis and developing targeted therapies. Hence, cellular pliancy relies on a dynamic cooperation between the cellular identity and the cellular context through epigenetic control, including the reactivation of cellular mechanisms, such as epithelial-to-mesenchymal transition (EMT). Such mechanisms and pathways confer plasticity to the cell allowing it to adapt to a hostile environment in a context of tumor initiation, thus changing its cellular identity.</div><div>Indeed, growing evidence suggests that cancer is a disease of cell identity crisis, whereby differentiated cells lose their defined identity and gain progenitor characteristics. The loss of cell fate commitment is a central feature of tumorigenesis and appears to be a prerequisite for neoplastic transformation. In this context, EMT-inducing transcription factors (EMT-TFs) cooperate with mitogenic oncoproteins to foster malignant transformation. The aberrant activation of EMT-TFs plays an active role in tumor initiation by alleviating key oncosuppressive mechanisms and by endowing cancer cells with stem cell-like properties, including the ability to self-renew, thus changing the course of tumorigenesis. This highly dynamic phenotypic change occurs concomitantly to major epigenome reorganization, a key component of cell differentiation and cancer cell plasticity regulation.</div><div>The concept of pliancy was initially proposed to address a fundamental question in cancer biology: why are some cells more likely to become cancerous in response to specific oncogenic events at particular developmental stages? We propose the concept of epipliancy, whereby a difference in epigenetic configuration leads to malignant transformation following an oncogenic insult. Here, we present recent studies furthering our understanding of how the epigenetic landscape may impact the modulation of cellular pliancy during early stages of cancer initiation.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 3","pages":"Article 189307"},"PeriodicalIF":9.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761054","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":"Unraveling the kinase code: Role of protein kinase in lung cancer pathogenesis and therapeutic strategies","authors":"Mariyam Fatma ,&nbsp;Sana Parveen ,&nbsp;Snober S. Mir","doi":"10.1016/j.bbcan.2025.189309","DOIUrl":"10.1016/j.bbcan.2025.189309","url":null,"abstract":"<div><div>Lung cancer is a prominent cause of cancer-related deaths globally, prompting exploration into the molecular pathways governing cancer cell signaling. Recent insights highlight the critical role of kinases in carcinogenesis and metastasis, particularly in non-small cell lung cancer (NSCLC), where protein kinases significantly contribute to drug resistance. These diverse enzymes catalyze protein phosphorylation and are implicated in cancer through misregulated expression, amplification, aberrant phosphorylation, mutations, and chromosomal translocations. Amplifications of kinases serve as important diagnostic, prognostic, and predictive biomarkers across various cancers. Notably, the Phosphatidylinositol 3-kinase (PI3K)/AKT pathway is crucial for the survival and proliferation of tumor cells. Novel therapeutic approaches are being explored to precisely target these pathways. Peptide-based therapies offer specificity and reduced toxicity compared to conventional treatments, while gene therapy targets abnormal genetic expressions. Advances in nanotechnology and CRISPR/Cas9 systems enhance gene delivery methods, holding promise for targeting specific molecular pathways in lung cancer treatment and minimizing systemic toxicity.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 3","pages":"Article 189309"},"PeriodicalIF":9.7,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766076","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":"Some unanswered questions about the pyrimidine catabolic pathway: The human macrophage perspective","authors":"Arnaud Millet","doi":"10.1016/j.bbcan.2025.189306","DOIUrl":"10.1016/j.bbcan.2025.189306","url":null,"abstract":"<div><div>Pyrimidine catabolism has attracted attention in relation to pyrimidine analogs used as anticancer drugs but the absence of a severe phenotype associated with pyrimidine catabolism byproducts did not favor to pursue these efforts. Recently, the discovery that dihydropyrimidine dehydrogenase (DPD) has an oxygen-dependent expression in human macrophages brings the aforementioned pathway to the forefront. Moreover, the finding that thymidine phosphorylase, the direct upstream enzyme to DPD in the pathway, also has a huge expression level in macrophages puts a new perspective on this pathway suggesting to look again at the physiology of intracellular pyrimidine bases catabolism revealing some unanswered questions. In this review, we propose to reassess the known and unknown of the catabolism of pyrimidine base in the light of these new results obtained in human macrophages.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 3","pages":"Article 189306"},"PeriodicalIF":9.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738806","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":"Decoding the genetic puzzle: Mutations in key driver genes of pancreatic neuroendocrine tumors","authors":"Huanchang Jiang ,&nbsp;Wuhu Zhang ,&nbsp;Xiaowu Xu,&nbsp;Xianjun Yu,&nbsp;Shunrong Ji","doi":"10.1016/j.bbcan.2025.189305","DOIUrl":"10.1016/j.bbcan.2025.189305","url":null,"abstract":"<div><div>Although pancreatic neuroendocrine tumors (PanNETs) are less common than other pancreatic tumors, they show significant differences in clinical behavior, genetics, and treatment responses. The understanding of the molecular pathways of PanNETs has gradually improved with advances in sequencing technology. Mutations in <em>MEN1</em> (the most frequently varied gene) may result in the deletion of the tumor suppressor menin, affecting gene regulation, DNA repair, and chromatin modification. Changes in ATRX and DAXX involve chromatin remodeling, telomere stability and are associated with the alternative lengthening of telomeres (ALT) pathway and aggressive tumors. <em>VHL</em> mutations emphasize the roles of hypoxia and angiogenesis. Mutations in <em>PTEN</em>, <em>TSC1/TSC2</em>, and <em>AKT1–3</em> often disrupt the mTOR pathway, complicating the genetic landscape of PanNETs. Understanding these genetic alterations and their impact on the PI3K/AKT/mTOR axis help to investigate new targeted therapies, which in turn can improve patient prognosis. This review aims to clarify PanNET pathogenesis through key mutations and their clinical relevance.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 3","pages":"Article 189305"},"PeriodicalIF":9.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738805","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":"The role and application of Coronin family in human tumorigenesis and immunomodulation","authors":"Huimeng Gao ,&nbsp;Fuli Sun ,&nbsp;Xuanyu Zhang ,&nbsp;Xue Qiao ,&nbsp;Yan Guo","doi":"10.1016/j.bbcan.2025.189304","DOIUrl":"10.1016/j.bbcan.2025.189304","url":null,"abstract":"<div><div>The Coronin family, a class of actin-binding proteins involved in the formation and maintenance of cytoskeleton structural stability, is aberrantly expressed in various tumors, including lung, gastric and head and neck cancers. They can regulate tumor cell metabolism and proliferation through RAC-1 and Wnt/β-Catenin signaling pathways and regulate invasion by influencing the PI3K, PAK4, and MT1-MMP signaling pathways and impacting the actin-network dynamics. In recent years, an increasing number of studies have highlighted the crucial roles of the cytoskeleton and immune modulation in the occurrence and development of tumors. The article delves into the Coronin family's pivotal role in tumor immune evasion, highlighting its modulation of neutrophil, T cell, and vesicular transport functions, as well as its interactions with tumorigenesis related organelles such as the endoplasmic reticulum, Golgi apparatus, mitochondria, and lysosomes. It also summarizes the potential therapeutic applications of the Coronin family in oncology. This review provides valuable insights into the mechanisms through which the Coronin family is implicated in the onset and progression of tumors. It also provides more theoretical foundation for tumor immunotherapy and combination drug therapy.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 3","pages":"Article 189304"},"PeriodicalIF":9.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738804","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":"MicroRNAs and lysosomal membrane proteins: Critical interactions in tumor progression and therapy","authors":"Jiahao Xu ,&nbsp;Shiqiang Liu ,&nbsp;Yujie Jin ,&nbsp;Lizhuo Wang ,&nbsp;Jialin Gao","doi":"10.1016/j.bbcan.2025.189303","DOIUrl":"10.1016/j.bbcan.2025.189303","url":null,"abstract":"<div><div>Cancer development is influenced by genetic and epigenetic variations, with the interactions between microRNAs (miRNAs) and lysosomal membrane proteins (LMPs) representing key regulatory mechanisms with potential as therapeutic targets. This review focuses on the complex regulatory mechanisms of miRNAs and LMPs in tumor progression, specifically highlighting their roles in tumor suppression, tumor promotion, tumor therapy, and drug resistance and their future application in treatment strategies. Overall, the interactions of LMPs with miRNAs have critical roles in tumor regulation, and studies of these interactions will further highlight their molecular contributions to cancer development.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 3","pages":"Article 189303"},"PeriodicalIF":9.7,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712470","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":"Radiotherapy modulates autophagy to reshape the tumor immune microenvironment to enhance anti-tumor immunity in esophageal cancer","authors":"Suna Zhou,&nbsp;Haihua Yang","doi":"10.1016/j.bbcan.2025.189302","DOIUrl":"10.1016/j.bbcan.2025.189302","url":null,"abstract":"<div><div>The combination of radiotherapy and immunotherapy exerts synergistic antitumor in a range of human cancers, and also in esophageal cancer. Radiotherapy-induced tumor immune microenvironment (TIME) reprogramming is an essential basis for the synergistic antitumor between radiotherapy and immunotherapy. Radiotherapy can induce autophagy in tumor cells and immune cells of TIME, and autophagy activation is involved in the modification of immunological characteristics of TIME. The TIME landscape of esophageal cancer, especially ESCC, can be affected by radiotherapy or autophagy regulation. In this review, we depicted that local radiotherapy-induced autophagy could promote the maturation, migration, infiltration, and function of immune cells by complicated mechanisms to make TIME from immune “cold” to “hot”, resulting in the synergistic antitumor of RT and IO. We argue that unraveling the relevance of radiotherapy-initiated autophagy to driving radiotherapy reprogramming TIME will open new ideas to explore new targets or more efficiently multimodal therapeutic interventions in ESCC.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 3","pages":"Article 189302"},"PeriodicalIF":9.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680284","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":"Exosomes: Traversing the blood-brain barrier and their therapeutic potential in brain cancer","authors":"Xiaopei Zhang ,&nbsp;Nichole Artz ,&nbsp;Dennis A. Steindler ,&nbsp;Shawn Hingtgen ,&nbsp;Andrew Benson Satterlee","doi":"10.1016/j.bbcan.2025.189300","DOIUrl":"10.1016/j.bbcan.2025.189300","url":null,"abstract":"<div><div>The blood-brain barrier (BBB) presents a major challenge for the effective delivery of therapeutic agents to the brain tumor cells from the peripheral blood circulation, making the treatment of central nervous system (CNS)-related cancers more difficult and resistant to both standard treatments and emerging therapies. Exosomes, which serve as messengers for intercellular communication throughout the body, can naturally or be modified to penetrate the BBB. Recently, exosomes have been increasingly explored as an invasive or non-invasive approach for delivering therapeutic agents to the CNS. With their low immunogenicity, ease of modification, excellent cargo protection, and inherent ability to cross the BBB, exosomes hold great promise for revolutionizing targeted therapy for CNS-related diseases, including brain cancer. In this review, we highlight recent discoveries and insights into the mechanisms exosomes use to penetrate the BBB, the methods they employ to payload diverse therapeutics, and their roles in transporting therapeutic compounds for brain cancer and other neurological disorders.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 3","pages":"Article 189300"},"PeriodicalIF":9.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652556","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":"Emerging importance of m6A modification in liver cancer and its potential therapeutic role","authors":"Tao Chen ,&nbsp;Wufei Ye ,&nbsp;Songsen Gao ,&nbsp;Yueran Li ,&nbsp;Jiajie Luan ,&nbsp;Xiongwen Lv ,&nbsp;Sheng Wang","doi":"10.1016/j.bbcan.2025.189299","DOIUrl":"10.1016/j.bbcan.2025.189299","url":null,"abstract":"<div><div>Liver cancer refers to malignant tumors that form in the liver and is usually divided into several types, the most common of which is hepatocellular carcinoma (HCC), which originates in liver cells. Other rare types of liver cancer include intrahepatic cholangiocarcinoma (iCCA). m6A modification is a chemical modification of RNA that usually manifests as the addition of a methyl group to adenine in the RNA molecule to form N6-methyladenosine. This modification exerts a critical role in various biological processes by regulating the metabolism of RNA, affecting gene expression. Recent studies have shown that m6A modification is closely related to the occurrence and development of liver cancer, and m6A regulators can further participate in the pathogenesis of liver cancer by regulating the expression of key genes and the function of specific cells. In this review, we provided an overview of the latest advances in m6A modification in liver cancer research and explored in detail the specific functions of different m6A regulators. Meanwhile, we deeply analyzed the mechanisms and roles of m6A modification in liver cancer, aiming to provide novel insights and references for the search for potential therapeutic targets. Finally, we discussed the prospects and challenges of targeting m6A regulators in liver cancer therapy.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 3","pages":"Article 189299"},"PeriodicalIF":9.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635022","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}