Critical reviews in oncology/hematology最新文献

{"title":"Polyploid giant cancer cells: Underlying Mechanisms, Signaling Pathways, and Therapeutic Strategies.","authors":"Gazmend Temaj, Sarmistha Saha, Silvia Chichiarelli, Pelin Telkoparan-Akillilar, Nexhibe Nuhii, Rifat Hadziselimovic, Luciano Saso","doi":"10.1016/j.critrevonc.2025.104802","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2025.104802","url":null,"abstract":"<p><p>Polyploid giant cancer cells (PGCCs) are characterized by enlarged nuclei, association with tumors, and resistance to treatment, contributing significantly to cellular heterogeneity. These cells arise from endoreplication and cell fusion, often triggered by stressors such as radiation and chemotherapy. PGCCs exhibit chromosomal instability and aneuploidy, leading to poor prognosis in various cancers. Key features include the ability to produce progeny cells via amitotic division and the expression of cancer stem cell markers. PGCC formation and function involve signaling pathways like cell fusion (GCM1/syncytin-1), cell cycle control, stress response, and EMT. Understanding these pathways is crucial for identifying therapeutic targets. Current therapeutic strategies targeting PGCCs involve drugs like azacitidine, decitabine, and zoledronic acid, as well as DNMT inhibitors in combination therapies. These approaches aim to reverse drug resistance and enhance antitumor efficacy. Furthermore, microRNAs (miRNAs) are pivotal in regulating gene expression and influencing the cell cycle, proliferation, and apoptosis. Cataloging miRNAs and understanding their function is critical for developing potential cancer treatments. Researchers are exploring miRNA-based modulation of signaling pathways to block tumor growth. This review highlights the complex biology of PGCCs and emphasizes the need for targeted therapies to improve cancer treatment outcomes.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104802"},"PeriodicalIF":0.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The evolving landscape of hormone receptor-positive/HER2-negative metastatic breast cancer (EVOLVE): an Italian Delphi consensus report.","authors":"Federica Miglietta, Maria Grazia Razeti, Aldo Caltavituro, Arianna Dri, Carmine Valenza, Giampaolo Bianchini, Laura Biganzoli, Andrea Botticelli, Michele Caruso, Saverio Cinieri, Carmen Criscitiello, Carmine De Angelis, Michelino De Laurentis, Lucia Del Mastro, Sabino De Placido, Marzia Del Re, Maria Vittoria Dieci, Alessandra Fabi, Daniele Generali, Alessandra Gennari, Lorenzo Gerratana, Mario Giuliano, Matteo Lambertini, Umberto Malapelle, Luca Malorni, Icro Meattini, Ida Paris, Giancarlo Pruneri, Claudio Zamagni, Alberto Zambelli, Francois Clement Bidard, Valentina Guarneri, Fabio Puglisi, Giuseppe Curigliano, Grazia Arpino","doi":"10.1016/j.critrevonc.2025.104793","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2025.104793","url":null,"abstract":"<p><strong>Background: </strong>The expanding treatment landscape for patients with hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) has led to the emergence of new \"grey areas\" not covered by international guidelines, where treatment decision making is particularly challenging.</p><p><strong>Methods: </strong>Sixteen relevant statements regarding the management of HR+/HER2 mBC were formulated by an Executive Board and validated by a Scientific Board, composed by internationally recognized experts in the field of BC. Subsequently, 50 Italian oncologists were surveyed between May 2024 and June 2024 through the modified Delphi method, in order to capture their rate of agreement and disagreement on the proposed statements.</p><p><strong>Results: </strong>The consensus was reached for all 16 statements: 4 were related to resistance and sensitivity to CDK4/6 inhibitors and endocrine therapy, 6 to biomarkers for HR+/HER2- mBC, and 6 to treatment algorithm of HR+/HER2- mBC. The Panel critically and comprehensively discussed the most relevant results, especially regarding the statements with lower level of agreement (which ranged from 85.4% to 100%).</p><p><strong>Conclusions: </strong>The treatment of HR+/HER2- mBC is currently being reshaped due to the expansion of its pharmacopoeia, the better understanding of its molecular determinants and the validation of biomarkers for patient selection. This consensus addressed the most controversial questions related to treatment decision and reached the agreement in all statements.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104793"},"PeriodicalIF":0.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges facing CAR T-cell immunotherapy in multiple myeloma.","authors":"Wanyan Ouyang, Jian-Qing Mi","doi":"10.1016/j.critrevonc.2025.104803","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2025.104803","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapy has demonstrated considerable promise in patients with late-line refractory multiple myeloma (MM), and there has been commercial approval for its use in treating relapsed and/or refractory MM (RR MM). B-cell maturation antigen remains the most extensively studied CAR T-cell target in this disease, although several alternative antigens are also under active investigation. Despite the notable success of CAR T-cell therapy in the treatment of RR MM, challenges remain in improving response rates, extending the durability of remission, and reducing relapse after CAR T-cell therapy. Notably, the presence of high-risk disease features is strongly associated with worse outcomes after CAR T-cell therapy for RR MM. This review explores the underlying mechanisms of CAR T-cell therapy failure and outlines potential salvage strategies. In addition, based on this mechanistic understanding, we discuss emerging technologies and platforms aimed at improving CAR designs, enhancing the quality of cellular products, increasing antitumor activity, and reducing relapse and/or resistance. Moreover, several approaches are being developed to improve the safety of CAR T-cell therapy. Finally, we consider the potential for earlier application of CAR T-cell therapy in high-risk patients and propose strategies to improve clinical outcomes. Ongoing research is expected to expand the therapeutic potential of CAR T-cell therapy, particularly in patients with high-risk RR MM.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104803"},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Role of TERT in Thyroid Cancer: A Systematic Review.","authors":"Thais Maloberti, Andrea Repaci, Laura Poppi, Floriana Jessica Di Paola, Giulia Calafato, Sara Coluccelli, Francesca Carosi, Alessandra Colapinto, Simone Colombero, Giacomo Credi, Giovanni Tallini, Maria A Pantaleo, Margherita Nannini, Dario de Biase","doi":"10.1016/j.critrevonc.2025.104792","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2025.104792","url":null,"abstract":"<p><strong>Background: </strong>TERT gene mutations play critical roles in tumor progression and have important implications in several solid tumors, including thyroid carcinoma. This study aimed to evaluate the association between TERT promoter mutations and histology and clinical features of thyroid carcinoma (TC).</p><p><strong>Materials and methods: </strong>We performed an up-to-date systematic review and a comprehensive meta-analysis. Systematic searches were made on MEDLINE (via Pubmed) databases using relevant keywords, and articles published until November 1^st, 2024 were selected. A total of 54 studies and 17'021 samples are included in the meta-analysis. Relevant data for the meta-analysis was extracted, and for statistical analysis, chi-square calculation was used.</p><p><strong>Results: </strong>Thyroid carcinomas with the highest frequency of TERT mutations are Anaplastic thyroid carcinoma (55.8%) and Diffuse sclerosing variant of papillary thyroid carcinoma (60.4%). No TERT mutations founds in Benign neoplasm, NIFTP and Medullary thyroid carcinoma. Mutations with the highest frequency is c.-124C>T (chr5:1295228 - C228T). TERT mutations are statistically correlated with Stage III&IV, presence of metastasis, overall survival, recurrence and radioiodine-refractory.</p><p><strong>Conclusion: </strong>TERT mutation plays a crucial role as a prognostic biomarker with tumor aggressiveness. Thus, in clinical practice, mutational status assessment of the TERT promoter should be considered for accurate prognostic stratification of TCs.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104792"},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting c-MYC has a Key Role in Hepatocellular Carcinoma Therapy.","authors":"Peng Dai, Liping Wang","doi":"10.1016/j.critrevonc.2025.104786","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2025.104786","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a top cause of cancer-associated mortality worldwide, with limited effective treatment options. The oncogenic transcription factor c-MYC plays a pivotal role in HCC pathogenesis by regulating key cellular processes, including proliferation, metabolism, and apoptosis. Impaired c-MYC regulation strongly correlates with aberrant activation of multiple signaling pathways, such as PI3K/Akt/mTOR, Wnt/β-catenin, and MAPK/ERK, which collectively drive tumor progression. Furthermore, c-MYC facilitates metabolic reprogramming, enhancing glycolysis and glutamine metabolism to support rapid tumor growth. Recent advances highlight the critical interplay between c-MYC and epigenetic modulators, ubiquitination processes, and non-coding RNAs, which further sustain its oncogenic activity. Targeting c-MYC through direct inhibition, pathway-specific interventions, and combination therapies stands as a compelling option for HCC treatment. This review offers an in-depth overview of the molecular mechanisms governing c-MYC-driven hepatocarcinogenesis and explores emerging therapeutic approaches aimed at disrupting this oncogenic network. A deeper understanding of c-MYC's role in HCC will pave the way for novel treatment strategies with potential clinical applications.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104786"},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the Tumor Microenvironment on Progression and Treatment Response in Lymphoma and Chronic Lymphocytic Leukemia: A Systematic Review of the Literature.","authors":"Sebastian Villamizar Castellanos, Maria Paula Rodriguez Castellanos, Maria Camila Gil Avendaño, Mary Cielo Arias Asprilla, Miguel Santiago Garcia Leal, Gloria Tirado","doi":"10.1016/j.critrevonc.2025.104782","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2025.104782","url":null,"abstract":"<p><strong>Introduction: </strong>The tumor microenvironment (TME) plays a critical role in the progression of lymphomas and chronic lymphocytic leukemia (CLL). Comprising immune cells, cytokines, growth factors, and the extracellular matrix, it modulates therapeutic resistance and tumor aggressiveness. Key elements such as Tregs and TAMs induce immunosuppression, while cytokines like IL-6 promote malignant cell proliferation and survival.</p><p><strong>Objective: </strong>To synthesize evidence regarding the influence of the TME on the progression and treatment response in lymphoma and CLL, identifying knowledge gaps and potential therapeutic targets.</p><p><strong>Methods: </strong>A systematic review was conducted following PRISMA guidelines, including 17 studies published between 2000-2024 on the TME in lymphoma and CLL. Primary outcomes included overall survival (OS), progression-free survival (PFS), and treatment response rates. Searches included databases such as PubMed, Scopus, and Cochrane.</p><p><strong>Results: </strong>Elevated IL-6 levels were associated with worse OS in aggressive lymphomas (mean OS 43.3 months in IL-6 positive patients vs. 96.0 months in negative, p < 0.001). A high proportion of Tregs in the TME correlated with shorter PFS (53% at 5 years vs. 72%, p = 0.013). In CLL, treatment with BTK inhibitors favorably modified the Th2/Th1 ratio (p < 0.002), improving clinical responses.</p><p><strong>Discussion: </strong>The findings confirm the relevance of the TME as a determinant of clinical and prognostic heterogeneity. IL-6 and Tregs emerge as key biomarkers and therapeutic targets. Strategies aimed at reversing immunosuppression could optimize clinical outcomes; however, methodological limitations persist, such as heterogeneity in TME characterization methods.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104782"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between LDH and GLIM criteria for cancer cachexia: Systematic Review and Meta-Analysis.","authors":"Joshua Thompson, Josh McGovern, Campbell Roxburgh, Joanne Edwards, Ross D Dolan, Donald C McMillan","doi":"10.1016/j.critrevonc.2024.104378","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2024.104378","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer cachexia is a clinical condition characterized by recognizable \"sickness behaviors\" accompanied by loss of lean body tissue. The Global Leadership on Malnutrition (GLIM) has proposed phenotypic (unintentional weight loss, low body mass index and low muscle mass) and aetiologic (reduced food intake and inflammation or disease burden) diagnostic criteria. Recent work has suggested serum lactate dehydrogenase (LDH) might represent a 3^rd aetiologic criteria. Little is known of its relationship with GLIM. A systematic review and meta-analysis of their comparative prognostic value and association was performed.</p><p><strong>Methods: </strong>A search of electronic databases (PubMed, Medline, Ovid, Cochrane) up to February 2023 was used to identify studies that compared the prognostic value of LDH and components of the GLIM criteria in cancer. An analysis of the relationship between LDH and the components of GLIM was undertaken where this data was available. RevMan 5.4.1 was used to perform a meta-analysis for each diagnostic criteria that had 3 or more studies which reported hazard ratios with a 95 per cent confidence interval for overall survival (OS).</p><p><strong>Results: </strong>A total of 119 studies were reviewed. Advanced lung cancer was the most studied population. Included in the meta-analysis were 6 studies (n=2,165) on LDH and weight loss, 17 studies (n=7,540) on LDH and low BMI, 5 studies (n=758) on LDH and low muscle mass, 0 studies on LDH and food intake and 97 studies (n=37,185) on LDH and inflammation. There was a significant association between elevated serum LDH and each of low BMI (OR 1.39, 1.09 - 1.77; p=0.008), elevated NLR (OR 2.04, 1.57 - 2.65; p<0.00001) and elevated CRP (OR 2.58, 1.81 - 3.67; p<0.00001). There was no association between elevated serum LDH and low muscle mass. Only one study presented data on the association between LDH and unintentional weight loss. Elevated LDH showed a comparative OS (HR 1.86, 1.60 - 2.16; p<0.00001) to unintentional weight loss (HR 1.57, 1.23 - 1.99; p=0.0002) and had a similar OS (HR 2.01, 1.73 - 2.34; p<0.00001) to low BMI (HR 1.57, 1.29 -2.90; p<0.0001). LDH also showed an OS (HR 2.25, 1.76 - 2.87; p<0.00001) congruous with low muscle mass (HR 1.93, 1.14 - 3.27; p=0.01) and again, LDH conferred as poor an OS (HR 1.71, 1.60 - 1.82; p<0.00001) as elevated NLR (HR 1.57, 1.44 - 1.71; p<0.00001) or CRP (HR 1.53, 1.41 - 1.65; p<0.00001).</p><p><strong>Conclusion: </strong>Current literature suggests elevated serum LDH is associated with inflammation in cancer (an aetiologic GLIM criterion), however more work is required to establish the relationship between LDH and the phenotypic components of GLIM. Additionally, elevated serum LDH appears to be a comparative prognosticator of overall survival in cancer when compared to the GLIM criteria.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104378"},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Targeted Therapies and Strategies to Overcome Resistance in Biliary Tract Cancers.","authors":"T. Demir, Carolyn Moloney, D. Mahalingam","doi":"10.1016/j.critrevonc.2024.104388","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2024.104388","url":null,"abstract":"","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":"4 5","pages":"104388"},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140979580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tyrosine Kinase Inhibitors in Cancers: treatment optimization – Part I","authors":"David Combarel, Léa Dousset, Stéphane Bouchet, Florent Ferrer, Pauline Tetu, Céleste Lebbe, Joseph Ciccolini, Nicolas Meyer, Angelo Paci","doi":"10.1016/j.critrevonc.2024.104384","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2024.104384","url":null,"abstract":"","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":"44 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141043510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}