Critical reviews in oncology/hematology最新文献

{"title":"Management of ovarian reserve in breast cancer patients seeking pregnancies (MORE BREAKS): A Delphi consensus","authors":"Carlo Alviggi ,&nbsp;Giuseppe Gabriele Iorio ,&nbsp;Luigi Carbone ,&nbsp;Roberta Vallone ,&nbsp;Fedro Alessandro Peccatori ,&nbsp;Paola Anserini ,&nbsp;Filippo Maria Ubaldi ,&nbsp;Vito Trojano ,&nbsp;Nicola Colacurci ,&nbsp;Alessandro Conforti ,&nbsp;on behalf of Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES‑MR) and SIGO Special Interest Group on Infertility","doi":"10.1016/j.critrevonc.2025.104778","DOIUrl":"10.1016/j.critrevonc.2025.104778","url":null,"abstract":"<div><div>Breast cancer is one of the most common tumors among women with 10 % of cases diagnosed in reproductive age. Estrogen positive forms are characterized by an excellent long-term prognosis with the 5-year survival rate of approximately 90 %. Recently, the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in women good prognosis have been introduced. At present, there are no indications or protocols on the optimal management of conception during discontinuation of endocrine therapy for these patients. A Delphi consensus was carried out to obtain expert opinion from a global perspective to identify the optimal pathways to pursue childbearing with particular focus in strategies aimed at reducing time to live birth. The Delphi consensus was carried out involving one Scientific Coordinator and 6 additional experts. Each member of the Scientific Board suggested additional experts, resulting in a panel of 31 experts. The Scientific Board proposed 20 statements covering the following area of interest: 1) Resumption of menstrual cycle after the suspension of endocrine therapy; 2) Management of the washout period; 3) Fertility assessment; 4) Decision-making of reproductive planning; 5) Ovarian reserve evaluation; 6) Expectant management vs immediate fertility treatment; 6) Controlled ovarian stimulation protocols; 7) <em>In vitro</em> fertilization protocols. Eighteen statements reached the consensus This Delphi consensus provides strategies to reduce the time to live birth in breast cancer patients’ candidates for discontinuation of endocrine therapy.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104778"},"PeriodicalIF":5.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298291","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}

{"title":"T cell-mediated mechanisms of immune-related adverse events induced by immune checkpoint inhibitors","authors":"Lintong Li ,&nbsp;Yunfan Huang ,&nbsp;Ruzeng Xue ,&nbsp;Guomin Li ,&nbsp;Li Li ,&nbsp;Liuping Liang ,&nbsp;Kuan Lai ,&nbsp;Xiaowen Huang ,&nbsp;Yao Qin ,&nbsp;Yue Zheng","doi":"10.1016/j.critrevonc.2025.104808","DOIUrl":"10.1016/j.critrevonc.2025.104808","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs), which block inhibitory molecules such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death protein 1 (PD-1) or programmed death protein ligand 1 (PD-L1), have revolutionized cancer therapy. While ICIs confer significant clinical benefits in numerous cancer patients, they also induce multi-organ immune-mediated toxicities, collectively termed immune-related adverse events (irAEs). This review aims to elucidate the role of T cell subsets in driving irAEs pathogenesis. Emerging evidence demonstrates that irAEs-affected tissues exhibit dysregulated T cell subset activity, characterized by autoreactive T cell activation, Treg imbalance, helper T cell and memory T cell dysfunction. Similar to classic autoimmune diseases, aberrant T cell subset activity plays a vital role in irAEs pathogenesis. By synthesizing recent advances in the contributions of diverse T cell subsets, this review establishes T cell subset dysregulation as a cardinal pathological feature of irAEs, offering insights into T cell-targeted biomarkers and therapies to mitigate toxicity without compromising antitumor immunity.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104808"},"PeriodicalIF":5.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298292","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}

{"title":"The role of PIK3CA mutation in lobular breast cancer in the era of precision oncology – A systematic review","authors":"Christos Kavazis ,&nbsp;Anastasia Ekmektzoglou ,&nbsp;Athanasios Kokolakis ,&nbsp;Triantafyllos Liappis ,&nbsp;George Douganiotis ,&nbsp;Ioannis Natsiopoulos","doi":"10.1016/j.critrevonc.2025.104805","DOIUrl":"10.1016/j.critrevonc.2025.104805","url":null,"abstract":"<div><h3>Background</h3><div>Ιnvasive lobular carcinoma (ILC) is a distinct subtype of breast cancer with unique clinical and molecular features. Although ILC generally responds to endocrine therapy, it tends to exhibit lower chemotherapy sensitivity, underscoring the need for tailored therapeutic approaches. PIK3CA mutations are frequently observed in ILC. This systematic review evaluates the prevalence of PIK3CA mutations in ILC and examines their prognostic and predictive significance.</div></div><div><h3>Methods</h3><div>We searched PubMed and Scopus for studies reporting PIK3CA mutations in lobular breast cancer. Inclusion criteria encompassed studies on stage I–III ILC examining mutation frequency, prognosis, or predictive value. Data on mutation prevalence in ILC (and comparisons to invasive ductal carcinoma, IDC) and associated outcomes were extracted. Meta-analyses were performed with assessment of heterogeneity and publication bias.</div></div><div><h3>Results</h3><div>Ten relevant studies (nine cohorts) were included. The prevalence of PIK3CA mutations in ILC ranged from ∼30 % to ∼50 %. Statistic analysis showed that nearly half of ILCs harbor PIK3CA mutations. Mutation rates in ILC were generally higher than in IDC. No significant association between PIK3CA mutation status and patient prognosis was observed in the available studies. There were limited data ontreatment response.</div></div><div><h3>Conclusions</h3><div>PIK3CA is a commonly mutated gene in ILC, but current evidence does not demonstrate a clear impact on prognosis or definite predictive value for therapy response in this subtype. Nonetheless, the high mutation frequency provides a rationale for targeted therapeutic approaches. PIK3CA testing may be considered in advanced ILC to identify candidates for PI3K inhibitor therapy, although further research is needed.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"214 ","pages":"Article 104805"},"PeriodicalIF":5.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295519","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}

{"title":"Polyploid giant cancer cells: Underlying mechanisms, signaling pathways, and therapeutic strategies","authors":"Gazmend Temaj ,&nbsp;Sarmistha Saha ,&nbsp;Silvia Chichiarelli ,&nbsp;Pelin Telkoparan-Akillilar ,&nbsp;Nexhibe Nuhii ,&nbsp;Rifat Hadziselimovic ,&nbsp;Luciano Saso","doi":"10.1016/j.critrevonc.2025.104802","DOIUrl":"10.1016/j.critrevonc.2025.104802","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104802"},"PeriodicalIF":5.5,"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":2,"RegionCategory":"医学","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 ,&nbsp;Jian-Qing Mi","doi":"10.1016/j.critrevonc.2025.104803","DOIUrl":"10.1016/j.critrevonc.2025.104803","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104803"},"PeriodicalIF":5.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251328","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}

{"title":"Exploring the role of TERT in thyroid Cancer: A systematic review","authors":"Thais Maloberti ,&nbsp;Andrea Repaci ,&nbsp;Laura Poppi ,&nbsp;Floriana Jessica Di Paola ,&nbsp;Giulia Calafato ,&nbsp;Sara Coluccelli ,&nbsp;Francesca Carosi ,&nbsp;Alessandra Colapinto ,&nbsp;Simone Colombero ,&nbsp;Giacomo Credi ,&nbsp;Giovanni Tallini ,&nbsp;Maria A. Pantaleo ,&nbsp;Margherita Nannini ,&nbsp;Dario de Biase","doi":"10.1016/j.critrevonc.2025.104792","DOIUrl":"10.1016/j.critrevonc.2025.104792","url":null,"abstract":"<div><h3>Background</h3><div><em>TERT</em> 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 <em>TERT</em> promoter mutations and histology and clinical features of thyroid carcinoma (TC).</div></div><div><h3>Materials and methods</h3><div>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 1st, 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.</div></div><div><h3>Results</h3><div>Thyroid carcinomas with the highest frequency of <em>TERT</em> mutations are Anaplastic thyroid carcinoma (55.8 %) and Diffuse sclerosing variant of papillary thyroid carcinoma (60.4 %). No <em>TERT</em> mutations founds in Benign neoplasm, NIFTP and Medullary thyroid carcinoma. Mutations with the highest frequency is c.–124C&gt;T (chr5:1295228 - C228T). <em>TERT</em> mutations are statistically correlated with Stage III&amp;IV, presence of metastasis, overall survival, recurrence and radioiodine-refractory.</div></div><div><h3>Conclusion</h3><div><em>TERT</em> mutation plays a crucial role as a prognostic biomarker with tumor aggressiveness. Thus, in clinical practice, mutational status assessment of the <em>TERT</em> promoter should be considered for accurate prognostic stratification of TCs.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104792"},"PeriodicalIF":5.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251329","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}

{"title":"The evolving landscape of hormone receptor-positive/HER2-negative metastatic breast cancer (EVOLVE): An Italian Delphi consensus report","authors":"Federica Miglietta ,&nbsp;Maria Grazia Razeti ,&nbsp;Aldo Caltavituro ,&nbsp;Arianna Dri ,&nbsp;Carmine Valenza ,&nbsp;Giampaolo Bianchini ,&nbsp;Laura Biganzoli ,&nbsp;Andrea Botticelli ,&nbsp;Michele Caruso ,&nbsp;Saverio Cinieri ,&nbsp;Carmen Criscitiello ,&nbsp;Carmine De Angelis ,&nbsp;Michelino De Laurentis ,&nbsp;Lucia Del Mastro ,&nbsp;Sabino De Placido ,&nbsp;Marzia Del Re ,&nbsp;Maria Vittoria Dieci ,&nbsp;Alessandra Fabi ,&nbsp;Daniele Generali ,&nbsp;Alessandra Gennari ,&nbsp;Grazia Arpino","doi":"10.1016/j.critrevonc.2025.104793","DOIUrl":"10.1016/j.critrevonc.2025.104793","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 %).</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104793"},"PeriodicalIF":5.5,"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":2,"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 miR-429 in cancer: From biogenesis, signaling pathways, interactions with long non-coding RNAs, and function to therapeutic application","authors":"Ensiyeh Bahadoran ,&nbsp;Abouzar Babaei ,&nbsp;Reza Ranji ,&nbsp;Parisa Badameh ,&nbsp;Samira Sabzi ,&nbsp;Babak Rahmani ,&nbsp;Hadi Ebadi","doi":"10.1016/j.critrevonc.2025.104795","DOIUrl":"10.1016/j.critrevonc.2025.104795","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) have emerged as critical regulators of gene expression, playing pivotal roles in cancer biology. Among these, miR-429, a member of the miR-200 family, influences migration, metastasis, apoptosis, and cell proliferation, all of which are vital for controlling cancer biology. This review examined the biogenesis, regulation, and signaling pathways associated with miR-429, as well as its interactions with long non-coding RNAs (lncRNAs) and other molecular networks that contribute to tumorigenesis. We explore its diverse expression patterns across various malignancies, including renal cell carcinoma, esophageal cancer, breast cancer, lung cancer, and glioblastoma, highlighting its dual role in tumorigenesis and metastasis. Additionally, it addresses the clinical relevance of miR-429, assessing its potential as a biomarker for cancer diagnosis, prognosis, and its promising therapeutic implications. Through a detailed analysis of miR-429 expression patterns and their impact across different cancer types, this review highlights its complex mechanisms in different cancers and its potential for targeted cancer therapy.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104795"},"PeriodicalIF":5.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230207","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}

{"title":"The role of ATF3 in the crosstalk between cellular stress response and ferroptosis in tumors","authors":"Mingbo Jia ,&nbsp;Minghao Shi ,&nbsp;Yao Zhao ,&nbsp;Yao Li ,&nbsp;Xiaoyi Liu ,&nbsp;Liyan Zhao","doi":"10.1016/j.critrevonc.2025.104791","DOIUrl":"10.1016/j.critrevonc.2025.104791","url":null,"abstract":"<div><div>During cellular stress, which results in DNA damage, protein, glucose, and lipid metabolism disorders, and redox homeostasis imbalance, various cellular stress responses are triggered, such as DNA damage response, endoplasmic reticulum stress, integrated stress response, and oxidative stress. These cellular stress responses play an important role in the disease process and have a dual role. Activating transcription factor3 belongs to the ATF/CREB family and is activated by stress. It is a transcription factor that plays an important role in gene regulation. It mainly participates in the regulation of disease progression by regulating metabolic homeostasis. Its expression is related to the prognosis of various tumors. ATF3, which is elevated in tumor cells by stress stimulation, not only participates in the repair of internal environment homeostasis mediated by cellular stress response, but also plays a key role in programmed cell death mediated by cellular stress response. Cellular stress response can affect the occurrence of ferroptosis through multiple pathways, with ATF3 being a key protein. This review first introduces the mechanism of ATF3 expression regulation, then summarizes the dual role of ATF3 in DNA damage response, endoplasmic reticulum stress, integrated stress response, and oxidative stress. Finally, it emphasizes the mechanism of ATF3 affecting ferroptosis through DNA damage response, and ER and oxidative stress. This study comprehensively reviews the role of ATF3 in tumors from multiple perspectives, providing new directions for tumor treatment.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104791"},"PeriodicalIF":5.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236146","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}

{"title":"Targeting c-MYC has a key role in hepatocellular carcinoma therapy","authors":"Peng Dai ,&nbsp;Liping Wang","doi":"10.1016/j.critrevonc.2025.104786","DOIUrl":"10.1016/j.critrevonc.2025.104786","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104786"},"PeriodicalIF":5.5,"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":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}