Biochimica et biophysica acta. Reviews on cancer最新文献

{"title":"Multifaceted roles of neutrophils in tumor microenvironment","authors":"Xueyin Pan ,&nbsp;Qiang Wang ,&nbsp;Beicheng Sun","doi":"10.1016/j.bbcan.2024.189231","DOIUrl":"10.1016/j.bbcan.2024.189231","url":null,"abstract":"<div><div>Neutrophils, the most abundant leukocyte population in circulation, play a crucial role in detecting and responding to foreign cells, such as pathogens and tumor cells. However, the impact of neutrophils on cancer pathogenesis has been overlooked because of their short lifespan, terminal differentiation, and limited transcriptional activity. Within the tumor microenvironment (TME), neutrophils can be influenced by tumor cells or other stromal cells to acquire either protumor or antitumor properties via the cytokine environment. Despite progress in neutrophil-related research, a comprehensive understanding of tissue-specific neutrophil diversity and adaptability in the TME is still lacking, which poses a significant obstacle to the development of neutrophil-based cancer therapies. This review evaluated the current studies on the dual roles of neutrophils in cancer progression, emphasizing their importance in predicting clinical outcomes, and explored various approaches for targeting neutrophils in cancer treatment, including their potential synergy with cancer immunotherapy.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189231"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142756577","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":"Methyltransferases in cancer drug resistance: Unlocking the potential of targeting SMYD3 to sensitize cancer cells","authors":"Paola Sanese ,&nbsp;Candida Fasano ,&nbsp;Martina Lepore Signorile ,&nbsp;Katia De Marco ,&nbsp;Giovanna Forte ,&nbsp;Vittoria Disciglio ,&nbsp;Valentina Grossi ,&nbsp;Cristiano Simone","doi":"10.1016/j.bbcan.2024.189203","DOIUrl":"10.1016/j.bbcan.2024.189203","url":null,"abstract":"<div><div>Drug resistance is a significant challenge in oncology and is driven by various mechanisms, among which a crucial role is played by enhanced DNA repair. Thus, targeting DNA damage response (DDR) factors with specific inhibitors is emerging as a promising therapeutic strategy. An important process involved in the modulation of DNA repair pathways, and hence in drug resistance, is post-translational modification (PTM). PTMs such as methylation affect protein function and are critical in cancer biology. Methylation is catalyzed by specific enzymes called protein methyltransferases. In recent years, the SET domain-containing N-lysine methyltransferase SMYD3 has emerged as a significant oncogenic driver. It is overexpressed in several tumor types and plays a signal-dependent role in promoting gastrointestinal cancer formation and development. Recent evidence indicates that SMYD3 is involved in the maintenance of cancer genome integrity and contributes to drug resistance in response to genotoxic stress by regulating DDR mechanisms. Several potential SMYD3 interactors implicated in DNA repair, especially in the homologous recombination and non-homologous end-joining pathways, have been identified by <em>in silico</em> analyses and confirmed by experimental validation, showing that SMYD3 promotes DDR protein interactions and enzymatic activity, thereby sustaining cancer cell survival. Targeting SMYD3, in combination with standard or targeted therapy, shows promise in overcoming drug resistance in colorectal, gastric, pancreatic, breast, endometrial, and lung cancer models, supporting the integration of SMYD3 inhibition into cancer treatment regimens. In this review, we describe the role played by SMYD3 in drug resistance and analyze its potential as a molecular target to sensitize cancer cells to treatment.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189203"},"PeriodicalIF":9.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514566","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":"Targeting autophagy in urological system cancers: From underlying mechanisms to therapeutic implications","authors":"Ziyue Yuan ,&nbsp;Jiani He ,&nbsp;Zhijia Li ,&nbsp;Bo Fan ,&nbsp;Lan Zhang ,&nbsp;Xiaojun Man","doi":"10.1016/j.bbcan.2024.189196","DOIUrl":"10.1016/j.bbcan.2024.189196","url":null,"abstract":"<div><div>The urological system, including kidneys, ureters, bladder, urethra and prostate is known to be vital for blood filtration, waste elimination and electrolyte balance. Notably, urological system cancers represent a significant portion of global cancer diagnoses and mortalities. The current therapeutic strategies for early-stage cancer primarily involve resection surgery, which significantly affects the quality of life of patients, whereas advanced-stage cancer often relies on less effective chemo- or radiotherapy. Recently, accumulating evidence has revealed that autophagy, a crucial process in which excess organelles or inclusions within cells are removed to maintain cell homeostasis, has numerous links to urological system cancers. In this review, we focus on summarizing the underlying two-sided mechanisms of autophagy in urological system cancers. We also review the current clinical drugs targeting autophagy, which demonstrate significant potential in improving treatment outcomes for urological system cancers. In addition, we provide an overview of the research status of novel small molecule compounds targeting autophagy that are in the preclinical stages of investigation. Furthermore, drug combinations based on autophagy modulation strategies in urological system cancers are systematically summarized and discussed. These findings provide comprehensive new insight for the future discovery of more autophagy-related drug candidates.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189196"},"PeriodicalIF":9.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482911","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 of ferroptosis resistance in lymph-associated tumour metastasis","authors":"Xiaoyu Li ,&nbsp;Meng Tian ,&nbsp;Liuchunyang Yu ,&nbsp;JinXiu Qian ,&nbsp;Jue Yang ,&nbsp;Xiangpeng Wang ,&nbsp;Cheng Lu ,&nbsp;Cheng Xiao ,&nbsp;Yuanyan Liu","doi":"10.1016/j.bbcan.2024.189200","DOIUrl":"10.1016/j.bbcan.2024.189200","url":null,"abstract":"<div><div>Tumour metastasis is a crucial factor in determining clinically challenging tumours. In this respect, the lymphatic system may act as potential entry portals for tumour metastasis, whilst, clinical detection of tumour-infiltrated lymph nodes also indicates poorer prognosis and higher metastatic risk. Whether tumour cells gain ferroptosis resistance in lymph that make them exhibit a stronger propensity for lymphatic dissemination compared to hematogenous spread might be a breakthrough for elucidating lymph-associated tumour metastasis. This review discusses how the lymphatic system endows tumour cells with ferroptosis resistance character, which makes them more propensity for lymph node pre-metastasis and distant metastasis through lymphatic circulation. Comprehensively considering the distinct structure and property of lymph and the unique metabolic characteristics of tumours, all of the lymphatic vessels, intestinal lymph and lymph nodes collectively manipulate an intricate interaction with the hematogenous system and afford substances exchange with tumour cells and extracellular vesicles, upon which make a ferroptosis resistant microenvironment for subsequent metastasis in distant organs and lymph nodes.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189200"},"PeriodicalIF":9.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482915","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":"Dual roles of human endogenous retroviruses in cancer progression and antitumor immune response","authors":"Yang Yang,&nbsp;Surong Dong,&nbsp;Benshuai You,&nbsp;Chenglin Zhou","doi":"10.1016/j.bbcan.2024.189201","DOIUrl":"10.1016/j.bbcan.2024.189201","url":null,"abstract":"<div><div>Human endogenous retroviruses (HERVs) are a class of transposable elements formed by the integration of ancient retroviruses into the germline genome. They are inherited in a Mendelian manner and approximately constitute 8 % of the human genome. HERVs were considered as “junk DNA” for decades, but increasing evidence suggests that they play significant roles in pathological inflammation, neural differentiation, and oncogenesis. Specifically, HERVs expression has been implicated in several oncogenic processes and the formation of the tumor microenvironment. Indeed, the dual roles of HERVs in cancer, serving as both promoters of oncogenesis and forerunners of the innate antitumor immune response, remain a subject of debate. In this review, we will discuss how HERVs participate in cancer progression and how they are regulated. Our aim is to provide a comprehensive understanding of the fundamental properties and potential function of HERVs in propagating oncogenesis and activating the antitumor immune response. We hope that updated knowledge will reshape our understanding of the critical roles played by HERVs in human evolution and cancer progression.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189201"},"PeriodicalIF":9.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482909","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":"CD8+ T-cell exhaustion: Impediment to triple-negative breast cancer (TNBC) immunotherapy","authors":"Dandan Feng ,&nbsp;Dongqing Pu ,&nbsp;Jinlu Ren ,&nbsp;Ming Liu ,&nbsp;Zhen Zhang ,&nbsp;Zhiyong Liu ,&nbsp;Jingwei Li","doi":"10.1016/j.bbcan.2024.189193","DOIUrl":"10.1016/j.bbcan.2024.189193","url":null,"abstract":"<div><div>CD8⁺ T-cell exhaustion has been identified as a significant contributor to immunosuppression and immune escape in triple-negative breast cancer (TNBC). Dysfunction due to cell exhaustion is characterized by reduced effector capacity and sustained expression of inhibitory receptors (IRs). The factors contributing to CD8⁺ T-cell exhaustion are multifaceted, encompassing external influences such as the upregulation of IRs, reduction of effector cytokines, and internal changes within the immune cell, including transcriptomic alterations, epigenetic landscape remodeling, and metabolomic shifts. The impact of the altered TNBC tumor microenvironment (TME) on Tex is also a critical consideration. The production of exhausted CD8⁺ T-cells (CD8⁺ Tex) is positively correlated with poor prognosis and reduced response rates to immunotherapy in TNBC patients, underscoring the urgent need for the development of novel TNBC immunotherapeutic strategies that target the mechanisms of CD8⁺ T-cell exhaustion. This review delineates the dynamic trajectory of CD8⁺ T-cell exhaustion development in TNBC, provides an update on the latest research advancements in understanding its pathogenesis, and offers insights into potential immunotherapeutic strategies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189193"},"PeriodicalIF":9.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482913","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":"Modeling bladder cancer in the laboratory: Insights from patient-derived organoids","authors":"Zikai Guo ,&nbsp;Zhichao Li ,&nbsp;Jia Wang ,&nbsp;Hongxiao Jiang ,&nbsp;Xu Wang ,&nbsp;Yangyang Sun ,&nbsp;Weiren Huang","doi":"10.1016/j.bbcan.2024.189199","DOIUrl":"10.1016/j.bbcan.2024.189199","url":null,"abstract":"<div><div>Bladder cancer (BCa) is the most common malignant tumor of the urinary system. Current treatments often have poor efficacy and carry a high risk of recurrence and progression due to the lack of consideration of tumor heterogeneity. Patient-derived organoids (PDOs) are three-dimensional tissue cultures that preserve tumor heterogeneity and clinical relevance better than cancer cell lines. Moreover, PDOs are more cost-effective and efficient to cultivate compared to patient-derived tumor xenografts, while closely mirroring the tissue and genetic characteristics of their source tissues. The development of PDOs involves critical steps such as sample selection and processing, culture medium optimization, matrix selection, and improvements in culture methods. This review summarizes the methodologies for generating PDOs from patients with BCa and discusses the current advancements in drug sensitivity testing, immunotherapy, living biobanks, drug screening, and mechanistic studies, highlighting their role in advancing personalized medicine.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189199"},"PeriodicalIF":9.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482914","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 key role of matrix stiffness in colorectal cancer immunotherapy: mechanisms and therapeutic strategies","authors":"Engeng Chen ,&nbsp;Zhiru Zeng ,&nbsp;Wei Zhou","doi":"10.1016/j.bbcan.2024.189198","DOIUrl":"10.1016/j.bbcan.2024.189198","url":null,"abstract":"<div><div>Increased matrix stiffness within the colorectal cancer (CRC) tumor microenvironment (TME) has emerged as a pivotal determinant of immunotherapy outcomes. This review discusses the role of aberrant extracellular matrix (ECM) deposition and cross-linking in augmenting matrix stiffness, a phenomenon that not only scaffolds the tumor architecture but also contributes to tumorigenicity and immunologic evasion. Herein, we critically appraise the influence of matrix stiffness on the immunotherapeutic landscape of CRC, focusing on its capacity to impede therapeutic efficacy by modulating immune cell infiltration, activation, and functional performance. The review explores the molecular dynamics whereby matrix stiffness prompts tumor evolution, highlighting the integral role of integrin signaling, cancer-associated fibroblasts (CAFs), and the process of epithelial-mesenchymal transition (EMT). We bring to the fore the paradoxical impact of an indurated ECM on immune effector cells, chiefly T cells and macrophages, which are indispensable for immune surveillance and the execution of immunotherapeutic strategies, yet are markedly restrained by a fibrotic matrix. Furthermore, we examine how matrix stiffness modulates immune checkpoint molecule expression, thereby exacerbating the immunosuppressive milieu within the TME and attenuating immunotherapeutic potency. Emergent therapeutic regimens targeting matrix stiffness—including matrix modulators, inhibitors of mechanotransduction signaling pathways, and advanced biomaterials that mimic the ECM—proffer novel modalities to potentiate immunotherapy responsiveness. By refining the ECM's biomechanical attributes, the mechanical barriers posed by the tumor stroma can be improved, facilitating robust immune cell penetration and activity, and thereby bolstering the tumor's susceptibility to immunotherapy. Ongoing clinical trials are evaluating these innovative treatments, particularly in combination with immunotherapies, with the aim of enhancing clinical outcomes for CRC patients afflicted by pronounced matrix stiffness.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189198"},"PeriodicalIF":9.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445946","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":"Belling the “cat”: Wnt/β-catenin signaling and its significance in future cancer therapies","authors":"Akansha Goyal ,&nbsp;Satyajit Laxman Murkute ,&nbsp;Sujoy Bhowmik ,&nbsp;Chandra Prakash Prasad ,&nbsp;Purusottam Mohapatra","doi":"10.1016/j.bbcan.2024.189195","DOIUrl":"10.1016/j.bbcan.2024.189195","url":null,"abstract":"<div><div>The WNT/β-catenin is among one of the most extensively studied cellular signaling pathways involved in the initiation and progression of several deadly cancers. It is now understood that the WNT/β-catenin signaling, during tumor progression operates in a very complex fashion beyond the earlier assumed simple WNT ‘On’ or ‘Off’ mode as it recruits numerous WNT ligands, receptors, transcriptional factors and also cross-talks with other signaling molecules including the noncanonical WNT regulators. WNT/β-catenin signaling molecules are often mutated in different cancers which makes them very challenging to inhibit and sometimes ranks them among the undruggable targets. Furthermore, due to the evolutionary conservation of this pathway, inhibiting WNT/β-catenin has caused significant toxicity in normal cells. These challenges are reflected in clinical trial data, where the use of WNT/β-catenin inhibitors as standalone treatments remains limited. In this review, we have highlighted the crucial functional associations of diverse WNT/β-catenin signaling regulators with cancer progression and the phenotypic switching of tumor cells. Next, we have shed light on the roles of WNT/β-catenin signaling in drug resistance, clonal evolution, tumor heterogeneity, and immune evasion. The present review also focuses on various classes of routine and novel WNT/β-catenin therapeutic regimes while addressing the challenges associated with targeting the regulators of this complex pathway. In the light of multiple case studies on WNT/β-catenin inhibitors, we also highlighted the challenges and opportunities for future clinical trial strategies involving these treatments. Additionally, we have proposed strategies for future WNT/β-catenin-based drug discovery trials, emphasizing the potential of combination therapies and AI/ML-driven prediction approaches. Overall, here we showcased the opportunities, possibilities, and potentialities of WNT/β-catenin signaling modulatory therapeutic regimes as promising precision cancer medicines for the future.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189195"},"PeriodicalIF":9.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445947","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":"Perioperative immunotherapy for patients with EGFR mutant non-small cell lung cancer: Unexpected potential benefits","authors":"Feifei Teng ,&nbsp;Xiao Ju ,&nbsp;Zhenhua Gao ,&nbsp;Junhao Xu ,&nbsp;Yikun Li ,&nbsp;Yungang Wang ,&nbsp;Bingwen Zou ,&nbsp;Jinming Yu","doi":"10.1016/j.bbcan.2024.189194","DOIUrl":"10.1016/j.bbcan.2024.189194","url":null,"abstract":"<div><div>Given that immunotherapy has resulted in a significant overall survival (OS) benefit in advanced-stage disease, it is of notable interest to determine the effectiveness of these agents in early-stage non-small cell lung cancer (NSCLC). The potential exists for the immunotherapeutic approach in early-stage NSCLC to mirror the paradigm seen in advanced NSCLC, wherein survival enhancements have notably benefited the majority of patients. However, their performance in early-stage epidermal growth factor receptor (EGFR) mutant NSCLC is controversial. In the limited studies that included patients with EGFR mutation status, we found unexpected, good survival benefits of perioperative immune checkpoint inhibitors (ICIs) in resectable EGFR-positive NSCLC, which is controversial with those in advanced EGFR-mutant NSCLC. It is possible because of the shift toward immunosuppression that the immune environment undergoes during tumor progression. In the early disease stages, the anti-tumor immune response can be activated with fewer hindrances. In the context of EGFR mutant tumors, intratumor genetic heterogeneity can generate treatment-sensitive and -resistant subclones. The subclonality of the resistant subclone is pivotal in therapy response, with tyrosine kinase inhibitors (TKIs) selectively controlling EGFR-mutant cell proliferation and “competitive release” potentially explaining lower pathological responses in adjuvant TKIs trials. This review delves into emerging data on perioperative treatment modalities for early-stage EGFR mutant NSCLC, exploring unique mechanisms and predictive biomarkers to guide perioperative management strategies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189194"},"PeriodicalIF":9.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482910","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}