Pub Date : 2026-02-01Epub Date: 2025-12-05DOI: 10.1016/j.critrevonc.2025.105060
Yu Tian , Kaobin Ouyang , Hongsheng Wu , Haojie Liao , Lingjuan He , Tingting Luo , Keqiang Ma , Xiaowen Mao , Furong Wang , Hailin Xiong
Hepatocellular carcinoma (HCC) remains a major cause of cancer mortality due to profound heterogeneity and persistent therapeutic resistance. This review summarizes recent mechanistic advances showing how noncoding RNAs (ncRNAs)—including lncRNAs and circRNAs—cooperate with RNA-binding proteins (RBPs) to regulate ferroptosis, autophagy, lipid metabolism, immune evasion, and transcriptional programs. We highlight emerging principles involving RNA chemical modifications, structural elements, and liquid–liquid phase separation that define the specificity of ncRNA–RBP interactions. Recent multi-omics and spatial profiling technologies are also discussed for their role in revealing resistance-associated ncRNA–protein networks. Importantly, this review integrates these findings to outline actionable therapeutic opportunities and the translational potential of targeting ncRNA–RBP axes, emphasizing their relevance to precision oncology. By defining the key regulatory circuits that drive adaptive resistance, this work provides a conceptual framework that may guide biomarker development and personalized treatment strategies in HCC.
{"title":"Adaptive drug resistance mechanisms driven by non-coding RNA–protein interaction networks in hepatocellular carcinoma","authors":"Yu Tian , Kaobin Ouyang , Hongsheng Wu , Haojie Liao , Lingjuan He , Tingting Luo , Keqiang Ma , Xiaowen Mao , Furong Wang , Hailin Xiong","doi":"10.1016/j.critrevonc.2025.105060","DOIUrl":"10.1016/j.critrevonc.2025.105060","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) remains a major cause of cancer mortality due to profound heterogeneity and persistent therapeutic resistance. This review summarizes recent mechanistic advances showing how noncoding RNAs (ncRNAs)—including lncRNAs and circRNAs—cooperate with RNA-binding proteins (RBPs) to regulate ferroptosis, autophagy, lipid metabolism, immune evasion, and transcriptional programs. We highlight emerging principles involving RNA chemical modifications, structural elements, and liquid–liquid phase separation that define the specificity of ncRNA–RBP interactions. Recent multi-omics and spatial profiling technologies are also discussed for their role in revealing resistance-associated ncRNA–protein networks. Importantly, this review integrates these findings to outline actionable therapeutic opportunities and the translational potential of targeting ncRNA–RBP axes, emphasizing their relevance to precision oncology. By defining the key regulatory circuits that drive adaptive resistance, this work provides a conceptual framework that may guide biomarker development and personalized treatment strategies in HCC.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105060"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145703418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-25DOI: 10.1016/j.critrevonc.2025.105053
Ruo Lin , Boya Peng
Brain metastasis poses a formidable barrier in cancer management, characterized by delayed diagnosis and limited treatment options. Extracellular vesicles (EVs), nano-sized, lipid bilayer-bound particles secreted by virtually all cell types, have emerged as dual-functional agents with potential to revolutionize both diagnosis and treatment. Owing to their ability to cross the blood-brain barrier and circulate in bodily fluids, EVs serve as non-invasive reservoirs of tumor-derived biomarkers, offering new avenues for early and accurate diagnosis. Simultaneously, advances in EV engineering have enabled their use as targeted therapeutic vehicles capable of delivering chemotherapeutics, nucleic acids, or immunomodulators directly to metastatic brain lesions. Functionalization with brain-targeting ligands further enhances their specificity, reducing systemic toxicity and improving therapeutic precision. This review systematically explores the mechanistic roles of EVs in brain metastasis progression and highlights their transformative potential as both diagnostic tools and therapeutic nanocarriers, breaking current barriers in the clinical management of brain metastases.
{"title":"Breaking barriers: Extracellular vesicles as dual-agents in diagnosing and treating brain metastasis","authors":"Ruo Lin , Boya Peng","doi":"10.1016/j.critrevonc.2025.105053","DOIUrl":"10.1016/j.critrevonc.2025.105053","url":null,"abstract":"<div><div>Brain metastasis poses a formidable barrier in cancer management, characterized by delayed diagnosis and limited treatment options. Extracellular vesicles (EVs), nano-sized, lipid bilayer-bound particles secreted by virtually all cell types, have emerged as dual-functional agents with potential to revolutionize both diagnosis and treatment. Owing to their ability to cross the blood-brain barrier and circulate in bodily fluids, EVs serve as non-invasive reservoirs of tumor-derived biomarkers, offering new avenues for early and accurate diagnosis. Simultaneously, advances in EV engineering have enabled their use as targeted therapeutic vehicles capable of delivering chemotherapeutics, nucleic acids, or immunomodulators directly to metastatic brain lesions. Functionalization with brain-targeting ligands further enhances their specificity, reducing systemic toxicity and improving therapeutic precision. This review systematically explores the mechanistic roles of EVs in brain metastasis progression and highlights their transformative potential as both diagnostic tools and therapeutic nanocarriers, breaking current barriers in the clinical management of brain metastases.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105053"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-01-02DOI: 10.1016/j.critrevonc.2025.105111
Zixuan Yuan , Zhiwei Liu , Mengying Zhou , Huijuan Wen , Bei Li
Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype with no effective therapeutic targets. Recent advances in immunotherapy, particularly PD-1/PD-L1 inhibitors and CTLA-4 antibodies, have yielded promising clinical outcomes in some patients. Additionally, cell-based therapies and tumor vaccines show substantial potential. Evidence increasingly supports the superior efficacy of combination therapies integrating immunotherapy with antitumor agents over traditional monotherapies. Single-cell and spatial multi-omics technologies, including scRNA-seq and scATAC-seq, as well as spatial transcriptomics, have provided insights into how therapeutic agents remodel the tumor microenvironment (TME), revealing mechanisms of action and TNBC’s cellular heterogeneity. This review integrates the latest advances in single-cell multi-omics and pharmacology to summarize progress in TNBC immunotherapy development, highlighting new therapeutic targets and optimized drug combinations. Furthermore, it discusses how the TME influences immunotherapy resistance from a single-cell perspective. Overall, single-cell-guided immunotherapy represents an innovative approach for better clinical translation, advancing precision medicine, and potentially transforming clinical practice.
{"title":"Research progress on immunotherapeutics for triple-negative breast cancer from a single-cell perspective","authors":"Zixuan Yuan , Zhiwei Liu , Mengying Zhou , Huijuan Wen , Bei Li","doi":"10.1016/j.critrevonc.2025.105111","DOIUrl":"10.1016/j.critrevonc.2025.105111","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype with no effective therapeutic targets. Recent advances in immunotherapy, particularly PD-1/PD-L1 inhibitors and CTLA-4 antibodies, have yielded promising clinical outcomes in some patients. Additionally, cell-based therapies and tumor vaccines show substantial potential. Evidence increasingly supports the superior efficacy of combination therapies integrating immunotherapy with antitumor agents over traditional monotherapies. Single-cell and spatial multi-omics technologies, including scRNA-seq and scATAC-seq, as well as spatial transcriptomics, have provided insights into how therapeutic agents remodel the tumor microenvironment (TME), revealing mechanisms of action and TNBC’s cellular heterogeneity. This review integrates the latest advances in single-cell multi-omics and pharmacology to summarize progress in TNBC immunotherapy development, highlighting new therapeutic targets and optimized drug combinations. Furthermore, it discusses how the TME influences immunotherapy resistance from a single-cell perspective. Overall, single-cell-guided immunotherapy represents an innovative approach for better clinical translation, advancing precision medicine, and potentially transforming clinical practice.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105111"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Salivary duct carcinoma is a highly aggressive salivary gland malignancy characterized by rapid progression, early regional and distant metastasis, and poor clinical outcomes. Among the histopathological features associated with its aggressiveness, perineural invasion is of particular significance. Perineural invasion refers to the infiltration of tumor cells within or surrounding the perineural spaces and serves as an important route for tumor dissemination. In salivary duct carcinoma, the presence of perineural invasion has been identified as a negative prognostic indicator, correlating with increased risks of local recurrence, nodal involvement, and distant metastasis. Consequently, evaluation of perineural invasion is crucial in prognostication and treatment planning for patients with salivary duct carcinoma. A systematic review was conducted to evaluate the prevalence of perineural invasion in salivary duct carcinoma and to assess its impact on survival outcomes. Following PRISMA guidelines. PubMed, Scopus, Science direct and Embase were searched up to September, 2025 for studies on salivary duct carcinoma and its prognostic factors. Eligible studies were screened, data extracted, and quality assessed using the QUIPS Scale. Pooled estimates were calculated using a random-effects model. The pooled proportion of perineural invasion among salivary duct carcinoma cases was 0.54 (95 % CI: 0.45–0.63). Meta-analysis using a random-effects model demonstrated that the presence of PNI was significantly associated with poorer survival outcomes (HR = 1.64; 95 % CI: 1.01–2.68). For overall survival, PNI showed a trend towards adverse prognosis (HR = 1.67; 95 % CI: 0.80–3.48), while it emerged as a strong negative predictor for disease-free survival (HR = 3.32; 95 % CI: 1.77–6.23). Similarly, for disease-specific survival (HR = 1.48; 95 % CI: 0.23–9.48), progression-free survival (HR = 2.47), and distant recurrence (HR = 4.56), PNI was consistently associated with unfavorable outcomes, underscoring its role as a significant adverse prognostic factor in salivary duct carcinoma. Its presence is consistently associated with reduced survival and increased recurrence, emphasizing its prognostic importance in patient management.
{"title":"Prognostic significance of perineural invasion in salivary duct carcinoma: A systematic review and meta-analysis","authors":"Rezhat Abbas, Revathi Krishna, Jeyaseelan Augustine , Priya Kumar, Aadithya B. Urs","doi":"10.1016/j.critrevonc.2025.105104","DOIUrl":"10.1016/j.critrevonc.2025.105104","url":null,"abstract":"<div><div>Salivary duct carcinoma is a highly aggressive salivary gland malignancy characterized by rapid progression, early regional and distant metastasis, and poor clinical outcomes. Among the histopathological features associated with its aggressiveness, perineural invasion is of particular significance. Perineural invasion refers to the infiltration of tumor cells within or surrounding the perineural spaces and serves as an important route for tumor dissemination. In salivary duct carcinoma, the presence of perineural invasion has been identified as a negative prognostic indicator, correlating with increased risks of local recurrence, nodal involvement, and distant metastasis. Consequently, evaluation of perineural invasion is crucial in prognostication and treatment planning for patients with salivary duct carcinoma. A systematic review was conducted to evaluate the prevalence of perineural invasion in salivary duct carcinoma and to assess its impact on survival outcomes. Following PRISMA guidelines. PubMed, Scopus, Science direct and Embase were searched up to September, 2025 for studies on salivary duct carcinoma and its prognostic factors. Eligible studies were screened, data extracted, and quality assessed using the QUIPS Scale. Pooled estimates were calculated using a random-effects model. The pooled proportion of perineural invasion among salivary duct carcinoma cases was 0.54 (95 % CI: 0.45–0.63). Meta-analysis using a random-effects model demonstrated that the presence of PNI was significantly associated with poorer survival outcomes (HR = 1.64; 95 % CI: 1.01–2.68). For overall survival, PNI showed a trend towards adverse prognosis (HR = 1.67; 95 % CI: 0.80–3.48), while it emerged as a strong negative predictor for disease-free survival (HR = 3.32; 95 % CI: 1.77–6.23). Similarly, for disease-specific survival (HR = 1.48; 95 % CI: 0.23–9.48), progression-free survival (HR = 2.47), and distant recurrence (HR = 4.56), PNI was consistently associated with unfavorable outcomes, underscoring its role as a significant adverse prognostic factor in salivary duct carcinoma. Its presence is consistently associated with reduced survival and increased recurrence, emphasizing its prognostic importance in patient management.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105104"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-25DOI: 10.1016/j.critrevonc.2025.105099
Xiaojia Guo , Yuanyuan Xie , Rongmin Qian , Jing Li , Junling Shi , Qingsheng Huang , Dongyan Shao
Hepatocellular carcinoma (HCC) ranks among the most prevalent types of tumors globally. There is no effective cure for HCC in clinical practice, which emphasizes the need to conduct in-depth research into mechanisms that can facilitate the development of effective treatments for HCC. Numerous studies have demonstrated that the mechanical factors within an HCC microenvironment, such as matrix stiffness and fluid shear stress, have significant effects on the different stages of development. And these mechanical factors are also involved in the immune-evasion process of HCC, which affects the progression of HCC. However, current reviews related to HCC mainly focus on discussing the influence of mechanical factors on various cells in the tumor microenvironment, with less consideration of the impact of mechanical factors on each stage of tumor development. Therefore, this review discussed the influence of these different mechanical factors on the various stages of HCC development, including the initiation, proliferation, angiogenesis, migration, invasion, metastasis, drug resistance and immune escape. This review provides a theoretical basis for future in-depth investigations into the relationship between mechanical factors and HCC.
{"title":"Mechanical microenvironment and its role in hepatocellular carcinoma oncogenesis and progression","authors":"Xiaojia Guo , Yuanyuan Xie , Rongmin Qian , Jing Li , Junling Shi , Qingsheng Huang , Dongyan Shao","doi":"10.1016/j.critrevonc.2025.105099","DOIUrl":"10.1016/j.critrevonc.2025.105099","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) ranks among the most prevalent types of tumors globally. There is no effective cure for HCC in clinical practice, which emphasizes the need to conduct in-depth research into mechanisms that can facilitate the development of effective treatments for HCC. Numerous studies have demonstrated that the mechanical factors within an HCC microenvironment, such as matrix stiffness and fluid shear stress, have significant effects on the different stages of development. And these mechanical factors are also involved in the immune-evasion process of HCC, which affects the progression of HCC. However, current reviews related to HCC mainly focus on discussing the influence of mechanical factors on various cells in the tumor microenvironment, with less consideration of the impact of mechanical factors on each stage of tumor development. Therefore, this review discussed the influence of these different mechanical factors on the various stages of HCC development, including the initiation, proliferation, angiogenesis, migration, invasion, metastasis, drug resistance and immune escape. This review provides a theoretical basis for future in-depth investigations into the relationship between mechanical factors and HCC.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105099"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-12DOI: 10.1016/j.critrevonc.2025.105079
Dadi Shu , Zhaoming Chen , Baolin Li , Jing Wei , Jinbo Liu , Qiongying Hu
Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and ranks third in incidence among all cancer types. Among the treatment strategies for CRC, immunotherapy—particularly approaches targeting modulation of the tumor microenvironment (TME) to prevent immune escape—represents a key component. The interaction and influence between CRC cells and tumor-associated macrophages (TAMs) within the TME have been shown to be closely associated with immune escape and malignant progression in CRC. Among them, extracellular vesicles (EVs) derived from CRC cells (CRC-EVs) can be taken up by TAMs in the TME and regulate their polarization as well as the production of related bioactive substances. Conversely, EVs secreted by TAMs (TAMs-EVs) can be internalized by CRC cells, thereby promoting the malignant biological behaviors, including proliferation, metastasis, and resistance to radiotherapy and chemotherapy. In this review, we focus on the crosstalk between CRC cells and TAMs within the TME, summarizing and integrating current evidence on how CRC-EVs and TAMs-EVs contribute to TME remodeling and thereby influence CRC malignancy, while systematically outlining the cellular signaling pathways involved in this bidirectional communication.
{"title":"Crosstalk between tumor cells and tumor-associated macrophages mediated by extracellular vesicles: Research advances in remodeling the tumor microenvironment in colorectal cancer","authors":"Dadi Shu , Zhaoming Chen , Baolin Li , Jing Wei , Jinbo Liu , Qiongying Hu","doi":"10.1016/j.critrevonc.2025.105079","DOIUrl":"10.1016/j.critrevonc.2025.105079","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and ranks third in incidence among all cancer types. Among the treatment strategies for CRC, immunotherapy—particularly approaches targeting modulation of the tumor microenvironment (TME) to prevent immune escape—represents a key component. The interaction and influence between CRC cells and tumor-associated macrophages (TAMs) within the TME have been shown to be closely associated with immune escape and malignant progression in CRC. Among them, extracellular vesicles (EVs) derived from CRC cells (CRC-EVs) can be taken up by TAMs in the TME and regulate their polarization as well as the production of related bioactive substances. Conversely, EVs secreted by TAMs (TAMs-EVs) can be internalized by CRC cells, thereby promoting the malignant biological behaviors, including proliferation, metastasis, and resistance to radiotherapy and chemotherapy. In this review, we focus on the crosstalk between CRC cells and TAMs within the TME, summarizing and integrating current evidence on how CRC-EVs and TAMs-EVs contribute to TME remodeling and thereby influence CRC malignancy, while systematically outlining the cellular signaling pathways involved in this bidirectional communication.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105079"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cervical cancer (CC) is the fourth most common malignancy among women worldwide, highlighting the urgent need for improved predictive, diagnostic and prognostic biomarkers to enhance disease management and patient outcomes. Non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs), perform various functions in transcriptional, translational and post-translational regulation. Aberrant expression of ncRNAs in CC has been closely associated with disease initiation and progression, underscoring their potential as key regulators of cervical tumorigenesis. Several lncRNAs, such as HOTAIR and PVT1, contribute to cervical tumorigenesis by promoting cell proliferation, migration and invasion. Likewise, circRNAs, such as circ_0018289, act as miRNA sponges, leading to the dysregulation of key target genes. Moreover, specific miRNAs, such as miR-20a and miR-21, promote CC progression (oncogenic miRNAs), whereas others, including miR-214 and miR-218, exhibit a tumor suppressor role. Importantly, many ncRNAs are detectable in body fluids, representing stable and minimally invasive biomarkers suitable for liquid biopsy. Thus, in this comprehensive narrative review, we map the range of candidate ncRNAs reported in the literature and discuss their predictive, diagnostic, prognostic and therapeutic value, including their potential as circulating biomarkers in CC. We also highlight, as a future perspective, how integrated profiling approaches could guide research and support the development of non-invasive strategies for diagnosis, prognostic assessment, and therapy monitoring in CC.
{"title":"Non-coding RNAs and liquid biopsies: Emerging biomarkers for cervical cancer","authors":"Mariana Teixeira Costa , Valéria Tavares , Filomena Adega , Rui Medeiros","doi":"10.1016/j.critrevonc.2025.105091","DOIUrl":"10.1016/j.critrevonc.2025.105091","url":null,"abstract":"<div><div>Cervical cancer (CC) is the fourth most common malignancy among women worldwide, highlighting the urgent need for improved predictive, diagnostic and prognostic biomarkers to enhance disease management and patient outcomes. Non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs), perform various functions in transcriptional, translational and post-translational regulation. Aberrant expression of ncRNAs in CC has been closely associated with disease initiation and progression, underscoring their potential as key regulators of cervical tumorigenesis. Several lncRNAs, such as HOTAIR and PVT1, contribute to cervical tumorigenesis by promoting cell proliferation, migration and invasion. Likewise, circRNAs, such as circ_0018289, act as miRNA sponges, leading to the dysregulation of key target genes. Moreover, specific miRNAs, such as miR-20a and miR-21, promote CC progression (oncogenic miRNAs), whereas others, including miR-214 and miR-218, exhibit a tumor suppressor role. Importantly, many ncRNAs are detectable in body fluids, representing stable and minimally invasive biomarkers suitable for liquid biopsy. Thus, in this comprehensive narrative review, we map the range of candidate ncRNAs reported in the literature and discuss their predictive, diagnostic, prognostic and therapeutic value, including their potential as circulating biomarkers in CC. We also highlight, as a future perspective, how integrated profiling approaches could guide research and support the development of non-invasive strategies for diagnosis, prognostic assessment, and therapy monitoring in CC.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105091"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-16DOI: 10.1016/j.critrevonc.2025.105092
Fabio Salomone , Massimo Di Maio , Angela Viggiano , Luigi Liguori , Carminia Maria Della Corte , Giuseppe Viscardi , Fabiana Vitiello , Fabiana Napolitano , Antonio Santaniello , Antonio Nuccio , Simeone D’Ambrosio , Filippo Vitale , Annarita Avanzo , Alessandra Bulotta , Luigi Formisano , Roberto Ferrara , Roberto Bianco , Valter Torri , Alberto Servetto
Background
The ability of progression-free survival (PFS) and overall response rate (ORR) to predict overall survival (OS) outcomes in cancer trials is matter of debate. Herein, we investigated whether PFS and ORR predicted OS results in randomized clinical trials (RCTs) testing immune checkpoint inhibitors (ICIs) in advanced NSCLC.
Methods
ORR (ORORR,%ORR), OS (HROS,mOS) and PFS (HRPFS,mPFS) data were collected from phase III RCTs investigating ICIs in advanced NSCLC. Linear regression, weighted by sample size, between surrogate endpoints and OS were calculated. The power of correlation was defined by the value of coefficient of determination R2 (≥0.7 strong, 0.69–0.50 moderate, <0.5 weak).
Results
Forty investigational arms of ICIs ± chemotherapy (ChT) were identified for further investigation. Arm-level analysis revealed that mPFS had a strong correlation with mOS in all comparisons (R2=0.71), in ICIs+ChT trials (R2=0.81) and in first-line setting (R2=0.71). A weak correlation was found between mPFS-mOS (R2=0.48) in trials of ICIs without chemotherapy. Next, trial-level analysis revealed a weak correlation between HROS and HRPFS in all different groups, except in ICIs+ChT trial (R2=0.60). In addition, based on arm-level analysis, mOS and %ORR had moderate correlation in all comparisons (R2=0.58), in ICIs+ChT (R2=0.58) or ICIs (R2=0.53). In trial-level analysis, ORORR and HROS had moderate correlation (R2=0.55) in first-line setting and a strong correlation in ICIs+ChT trials (R2=0.79).
Conclusions
Across trials investigating ICIs in advanced NSCLC, PFS and ORR demonstrated various degrees of relationship with OS. Caution should be taken when efficacy of novel ICIs regimens is evaluated only using surrogate outcomes.
{"title":"Correlation of ORR and PFS with OS outcomes in phase III trials of immunotherapy in advanced NSCLC: Systematic review and meta-analysis","authors":"Fabio Salomone , Massimo Di Maio , Angela Viggiano , Luigi Liguori , Carminia Maria Della Corte , Giuseppe Viscardi , Fabiana Vitiello , Fabiana Napolitano , Antonio Santaniello , Antonio Nuccio , Simeone D’Ambrosio , Filippo Vitale , Annarita Avanzo , Alessandra Bulotta , Luigi Formisano , Roberto Ferrara , Roberto Bianco , Valter Torri , Alberto Servetto","doi":"10.1016/j.critrevonc.2025.105092","DOIUrl":"10.1016/j.critrevonc.2025.105092","url":null,"abstract":"<div><h3>Background</h3><div>The ability of progression-free survival (PFS) and overall response rate (ORR) to predict overall survival (OS) outcomes in cancer trials is matter of debate. Herein, we investigated whether PFS and ORR predicted OS results in randomized clinical trials (RCTs) testing immune checkpoint inhibitors (ICIs) in advanced NSCLC.</div></div><div><h3>Methods</h3><div>ORR (OR<sub>ORR</sub>,%ORR), OS (HR<sub>OS</sub>,mOS) and PFS (HR<sub>PFS</sub>,mPFS) data were collected from phase III RCTs investigating ICIs in advanced NSCLC. Linear regression, weighted by sample size, between surrogate endpoints and OS were calculated. The power of correlation was defined by the value of coefficient of determination R<sup>2</sup> (≥0.7 strong, 0.69–0.50 moderate, <0.5 weak).</div></div><div><h3>Results</h3><div>Forty investigational arms of ICIs ± chemotherapy (ChT) were identified for further investigation. Arm-level analysis revealed that mPFS had a strong correlation with mOS in all comparisons (R<sup>2</sup>=0.71), in ICIs+ChT trials (R<sup>2</sup>=0.81) and in first-line setting (R<sup>2</sup>=0.71). A weak correlation was found between mPFS-mOS (R<sup>2</sup>=0.48) in trials of ICIs without chemotherapy. Next, trial-level analysis revealed a weak correlation between HR<sub>OS</sub> and HR<sub>PFS</sub> in all different groups, except in ICIs+ChT trial (R<sup>2</sup>=0.60). In addition, based on arm-level analysis, mOS and %ORR had moderate correlation in all comparisons (R<sup>2</sup>=0.58), in ICIs+ChT (R<sup>2</sup>=0.58) or ICIs (R<sup>2</sup>=0.53). In trial-level analysis, OR<sub>ORR</sub> and HR<sub>OS</sub> had moderate correlation (R<sup>2</sup>=0.55) in first-line setting and a strong correlation in ICIs+ChT trials (R<sup>2</sup>=0.79).</div></div><div><h3>Conclusions</h3><div>Across trials investigating ICIs in advanced NSCLC, PFS and ORR demonstrated various degrees of relationship with OS. Caution should be taken when efficacy of novel ICIs regimens is evaluated only using surrogate outcomes.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105092"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-19DOI: 10.1016/j.critrevonc.2025.105097
Sergio Bracarda , Fabio Calabrò , Ugo De Giorgi , Giuseppe Procopio , Roberto Sabbatini , Camillo Porta
Background
Renal cell carcinoma (RCC), originating from renal tubular epithelial cells, represents approximately 80 % of all primary kidney tumors. Roughly 30 % of cases are diagnosed at an advanced stage, and a similar proportion experience recurrence after surgery for localized disease. This recurrence rate may improve with the recent introduction of an effective adjuvant immunotherapy.
Objective
This work aims to assess the current therapeutic landscape of metastatic RCC (mRCC), with a focus on immunotherapy-based combinations, and to offer expert, real-world insights into clinical decision-making and adverse event (AE) management.
Methods
Six oncologists specialized in mRCC completed a structured survey covering four key areas: (1) overall survival, (2) safety of IO–IO and IO–TKI combinations, (3) treatment selection, and (4) sequential strategies. Responses were reviewed in a virtual meeting, with agreement defined as concurrence by at least five of the six participants. Any areas without unanimous agreement were addressed through subsequent discussion rounds until a final agreement was reached.
Results
Nivolumab plus ipilimumab provides durable responses and long-term survival, especially in intermediate- and poor-risk patients. TKI-based combinations, including cabozantinib and lenvatinib, achieve strong disease control, while axitinib offers a greater dosing flexibility due to its short half-life. Toxicity profiles differ by regimen, requiring careful management of immune-related and TKI-associated adverse events. Relapse risk after adjuvant pembrolizumab should guide first-line therapy choice for advanced disease, while metastasis-directed treatments should be considered by multidisciplinary teams.
Conclusions
Optimal first-line treatment for mRCC requires consideration of patient characteristics, clinical and molecular prognostic factors, treatment tolerability, all of these parameters should be evaluated during a multidisciplinary team discussion.
{"title":"A daily clinical practice decision-making overview for the present metastatic renal cell carcinoma (mRCC) management landscape","authors":"Sergio Bracarda , Fabio Calabrò , Ugo De Giorgi , Giuseppe Procopio , Roberto Sabbatini , Camillo Porta","doi":"10.1016/j.critrevonc.2025.105097","DOIUrl":"10.1016/j.critrevonc.2025.105097","url":null,"abstract":"<div><h3>Background</h3><div>Renal cell carcinoma (RCC), originating from renal tubular epithelial cells, represents approximately 80 % of all primary kidney tumors. Roughly 30 % of cases are diagnosed at an advanced stage, and a similar proportion experience recurrence after surgery for localized disease. This recurrence rate may improve with the recent introduction of an effective adjuvant immunotherapy.</div></div><div><h3>Objective</h3><div>This work aims to assess the current therapeutic landscape of metastatic RCC (mRCC), with a focus on immunotherapy-based combinations, and to offer expert, real-world insights into clinical decision-making and adverse event (AE) management.</div></div><div><h3>Methods</h3><div>Six oncologists specialized in mRCC completed a structured survey covering four key areas: (1) overall survival, (2) safety of IO–IO and IO–TKI combinations, (3) treatment selection, and (4) sequential strategies. Responses were reviewed in a virtual meeting, with agreement defined as concurrence by at least five of the six participants. Any areas without unanimous agreement were addressed through subsequent discussion rounds until a final agreement was reached.</div></div><div><h3>Results</h3><div>Nivolumab plus ipilimumab provides durable responses and long-term survival, especially in intermediate- and poor-risk patients. TKI-based combinations, including cabozantinib and lenvatinib, achieve strong disease control, while axitinib offers a greater dosing flexibility due to its short half-life. Toxicity profiles differ by regimen, requiring careful management of immune-related and TKI-associated adverse events. Relapse risk after adjuvant pembrolizumab should guide first-line therapy choice for advanced disease, while metastasis-directed treatments should be considered by multidisciplinary teams.</div></div><div><h3>Conclusions</h3><div>Optimal first-line treatment for mRCC requires consideration of patient characteristics, clinical and molecular prognostic factors, treatment tolerability, all of these parameters should be evaluated during a multidisciplinary team discussion.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105097"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145806795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-09DOI: 10.1016/j.critrevonc.2025.105081
Eduardo Alvarado-Ortiz , Angela Patricia Moreno-Londoño , Miguel Ángel Sarabia-Sánchez
Current treatments for colorectal cancer (CRC) can induce apparent disease remission; unfortunately, CRC eventually relapses in many patients. CRC recurrence has been associated with the presence of dormant cancer cells, which are difficult to detect and are maintained in a resilient state characterized by a low cell cycling rate. Dormant cancer cells evade immune surveillance, are not eliminated by conventional therapy, and employ specific metabolic programs enabling them to remain hidden for extended periods. Furthermore, the period elapsed since the onset of the disease, represents the opportunity where tumor has early spread to distant sites. Importantly, cellular dormancy and awakening are also involved in metastasis. This review explores the nuanced mechanisms involved in cellular dormancy, from remnant cancer cells of the primary tumor to metastatic cancer cells. The insights in this field hold promise to contribute clinical innovations for the improvement of predictive biomarkers or targeted therapies. Indeed, we address cell dormancy by unifying a set of concepts from modern oncology in light of the unique characteristics of CRC. Here, we discuss the immune system, metabolic imbalance, and drug tolerance; the major challenges that dormant cancer cells must overcome once awakened. This review reinforces the translational value of cellular dormancy as the foremost cause of recurrence and poor prognosis in colorectal cancer, with the aim of guiding the development of potential emergent treatments that can be combined with existing approaches such as chemotherapy and immunotherapy.
{"title":"Dormancy in colorectal cancer: The functional core of resistance, metastasis, and relapse","authors":"Eduardo Alvarado-Ortiz , Angela Patricia Moreno-Londoño , Miguel Ángel Sarabia-Sánchez","doi":"10.1016/j.critrevonc.2025.105081","DOIUrl":"10.1016/j.critrevonc.2025.105081","url":null,"abstract":"<div><div>Current treatments for colorectal cancer (CRC) can induce apparent disease remission; unfortunately, CRC eventually relapses in many patients. CRC recurrence has been associated with the presence of dormant cancer cells, which are difficult to detect and are maintained in a resilient state characterized by a low cell cycling rate. Dormant cancer cells evade immune surveillance, are not eliminated by conventional therapy, and employ specific metabolic programs enabling them to remain hidden for extended periods. Furthermore, the period elapsed since the onset of the disease, represents the opportunity where tumor has early spread to distant sites. Importantly, cellular dormancy and awakening are also involved in metastasis. This review explores the nuanced mechanisms involved in cellular dormancy, from remnant cancer cells of the primary tumor to metastatic cancer cells. The insights in this field hold promise to contribute clinical innovations for the improvement of predictive biomarkers or targeted therapies. Indeed, we address cell dormancy by unifying a set of concepts from modern oncology in light of the unique characteristics of CRC. Here, we discuss the immune system, metabolic imbalance, and drug tolerance; the major challenges that dormant cancer cells must overcome once awakened. This review reinforces the translational value of cellular dormancy as the foremost cause of recurrence and poor prognosis in colorectal cancer, with the aim of guiding the development of potential emergent treatments that can be combined with existing approaches such as chemotherapy and immunotherapy.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"218 ","pages":"Article 105081"},"PeriodicalIF":5.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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