Medical Oncology最新文献

{"title":"Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.","authors":"Wenbo Liu, Xiangyan Jiang, Yong Ma, Huiguo Qing, Yingcun Bao, Zuoyi Jiao","doi":"10.1007/s12032-025-03053-0","DOIUrl":"https://doi.org/10.1007/s12032-025-03053-0","url":null,"abstract":"<p><p>The induction of replication stress has emerged as a potent strategy for cancer therapy, with alkylating agents, nucleoside analogs, and inhibitors of cyclin and cyclin-dependent kinase remaining prominent drugs. As mechanistic insights into responses to replication stress are evolving, novel therapeutic agents targeting replication stress response pathways have been progressively developed. Despite the demonstrated pharmacological and clinical efficacy of certain agents, the therapeutic landscape remains characterized by suboptimal patient prognoses. Mounting evidence implicates cancer cell metabolic reprogramming as a critical determinant in both modulating replication stress and attenuating genotoxic drug efficacy. In addition, some metabolic enzymes demonstrate non-canonical functions that potentiate DNA damage response, while some metabolic pathways contribute vulnerability to replication stress in malignant cells. Therefore, this review seeks to elucidate the mechanisms by which metabolic reprogramming modulates replication stress in cancer cells and to provide an overview of the latest advancements in therapeutic regimens development.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"494"},"PeriodicalIF":3.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective regulation and cellular metabolism by the lactate transporter MCT4 in GBM.","authors":"Sofian Al Shboul, Bingqiao Zhao, Estefania Esposito, Vanessza Fentor, Ashita Singh, Fraser Massie, Ted Hupp, Tessa Moses, Paul M Brennan, Kathryn Ball, Irena Dapic","doi":"10.1007/s12032-025-03060-1","DOIUrl":"https://doi.org/10.1007/s12032-025-03060-1","url":null,"abstract":"<p><p>Hypoxia drives adaptive gene expression in glioblastoma (GBM), influencing tumor progression and metabolic reprogramming. This study investigated the hypoxic response of a patient-derived GBM cancer stem cell line, identifying key hypoxia-inducible genes such as SLC16A3, CA9, BNIP3, VEGFA, and NDRG1. SLC16A3 encodes the lactate transporter MCT4, whose expression has been implicated in biology of several cancers, including GBM. To evaluate role of MCT4, its expression was transiently reduced using siRNA resulting in an attenuated hypoxic induction of NDRG1 and SOX2, while sparing CA9 and BNIP3. Immunoblotting of GBM patient tissues revealed heterogeneous co-expression of MCT4 and NDRG1, highlighting a possible metabolic diversity within tumors. Moreover, metabolomic data of the cells showed dysregulated metabolites such as elevated stearic acid and decreased levels of D-( +)-2-phosphoglyceric acid, lactic acid, purine, pyridoxal, N,N,N-trimethyl lysine, and phosphatidylcholine (18:1/18:1) (del9-trans). Decreased intracellular lactate and increased acidity under hypoxic conditions, confirmed important role of MCT4 role in lactate transport and pH regulation. By establishing central role of MCT4 in hypoxia-driven processes, this study provides valuable insights into GBM metabolic plasticity and suggests that MCT4 might be potential therapeutic target.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"497"},"PeriodicalIF":3.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theranostics in nuclear medicine: the era of precision oncology.","authors":"Noopur Gandhi, Ali M Alaseem, Rohitas Deshmukh, Artiben Patel, Omar Awad Alsaidan, Mohammad Fareed, Glowi Alasiri, Suhaskumar Patel, Bhupendra Prajapati","doi":"10.1007/s12032-025-03061-0","DOIUrl":"https://doi.org/10.1007/s12032-025-03061-0","url":null,"abstract":"<p><p>Theranostics represents a transformative advancement in nuclear medicine by integrating molecular imaging and targeted radionuclide therapy within the paradigm of personalized oncology. This review elucidates the historical evolution and contemporary clinical applications of theranostics, emphasizing its pivotal role in precision cancer management. The theranostic approach involves the coupling of diagnostic and therapeutic radionuclides that target identical molecular biomarkers, enabling simultaneous visualization and treatment of malignancies such as neuroendocrine tumors (NETs), prostate cancer, and differentiated thyroid carcinoma. Key theranostic radiopharmaceutical pairs, including Gallium-68-labeled DOTA-Tyr3-octreotate (Ga-68-DOTATATE) with Lutetium-177-labeled DOTA-Tyr3-octreotate (Lu-177-DOTATATE), and Gallium-68-labeled Prostate-Specific Membrane Antigen (Ga-68-PSMA) with Lutetium-177-labeled Prostate-Specific Membrane Antigen (Lu-177-PSMA), exemplify the \"see-and-treat\" principle central to this modality. This article further explores critical molecular targets such as somatostatin receptor subtype 2, prostate-specific membrane antigen, human epidermal growth factor receptor 2, CD20, and C-X-C chemokine receptor type 4, along with design principles for radiopharmaceuticals that optimize target specificity while minimizing off-target toxicity. Advances in imaging platforms, including positron emission tomography/computed tomography (PET/CT), single-photon emission computed tomography/CT (SPECT/CT), and hybrid positron emission tomography/magnetic resonance imaging (PET/MRI), have been instrumental in accurate dosimetry, therapeutic response assessment, and adaptive treatment planning. Integration of artificial intelligence (AI) and radiomics holds promise for enhanced image segmentation, predictive modeling, and individualized dosimetric planning. The review also addresses regulatory, manufacturing, and economic considerations, including guidelines from the United States Food and Drug Administration (USFDA) and European Medicines Agency (EMA), Good Manufacturing Practice (GMP) standards, and reimbursement frameworks, which collectively influence global adoption of theranostics. In summary, theranostics is poised to become a cornerstone of next-generation oncology, catalyzing a paradigm shift toward biologically driven, real-time personalized cancer care that seamlessly links diagnosis and therapy.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"498"},"PeriodicalIF":3.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review on the role of acetamido as a linker for the design and discovery of anticancer agents.","authors":"Amit Shimpi, Kapil Juvale","doi":"10.1007/s12032-025-03043-2","DOIUrl":"https://doi.org/10.1007/s12032-025-03043-2","url":null,"abstract":"<p><p>Cancer is the most significant health problem for mankind, causing millions of deaths every year. After the discovery of chemotherapy, conventional treatments have rapidly developed drug resistance, which has led to the search for novel and more effective anticancer agents. Different linkers have played a crucial role in the design of drugs due to their improved selectivity, physicochemical properties, and therapeutic efficacy. Among these linkers, the acetamido linker has emerged as a promising strategic pathway for enhancing the anticancer potency of drug candidates. Introducing an acetamido linker into the molecular scaffold strategically enhances the pharmacokinetics, stability, and selectivity of anticancer drugs, thus making it more precisely targeted to tumor cells. Acetamido groups have been reported to modulate the interaction between the drug and its molecular targets, enhancing cytotoxicity against a range of cancer cell lines, including different cancer traits. This review discusses the emerging role of acetamido linkers in anticancer drug design, focusing on SAR analysis and their therapeutic effects based on IC₅₀ values against various enzymes and human cancer cell lines. It also provides valuable insights into molecule target interactions, optimisation of various scaffolds for developing safer, more potent, and targeted anticancer therapeutics and an insight into the mechanistic role of acetamido linkers in drug-target interaction. This review underpins the key role of the acetamido linker in the development of new anticancer agents.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"496"},"PeriodicalIF":3.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epitranscriptomic sculpting: the role of m⁶A in alternative splicing, cancer progression, and methodological insights.","authors":"Farag Altalbawy, Eman Raeed Azzam, Ali Alkhathami, Ahmed Hussn, H Malathi, Akanksha Bhatt, Aman Shankhyan, Priya Priyadarshini Nayak, Sami Almalki, Mohammed Jawad Alnajar","doi":"10.1007/s12032-025-03045-0","DOIUrl":"https://doi.org/10.1007/s12032-025-03045-0","url":null,"abstract":"<p><p>The burgeoning field of epitranscriptomics -modifications of RNA molecules that do not alter the underlying RNA sequence but affect gene expression- has unveiled m⁶A as a pivotal modulator of RNA fate, with profound implications for alternative splicing and cancer progression. This review synthesizes current evidence delineating the molecular mechanisms by which m⁶A deposition influences spliceosomal dynamics and RNA processing. Central to this process is the coordinated action of m⁶A \"writers,\" \"erasers,\" and binding proteins (\"readers\"), which collectively dictate transcriptome diversity through precise modulation of splicing decisions. Aberrant m⁶A modifications have been increasingly correlated with dysregulated splicing patterns that contribute to oncogenic transformation, tumor heterogeneity, and the emergence of aggressive cancer phenotypes. By integrating findings from recent studies, this article highlights the critical interplay between epitranscriptomic regulation and the alternative splicing machinery, underscoring how these interactions drive pathophysiological processes in cancer. Furthermore, the review explores emerging therapeutic opportunities targeting the m⁶A regulatory network, calling attention to its potential as both a prognostic biomarker and a novel intervention point in precision oncology. Through a comprehensive examination of the current literature, this analysis provides valuable insights into the role of m⁶A in sculpting the cancer transcriptome, offering a robust framework for future research endeavors in the field of cancer biology and therapeutic innovation.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"492"},"PeriodicalIF":3.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic lymphocytic leukemia: criteria for first-line therapeutic choice-an opinion paper.","authors":"José Carda, Ângelo Martins, Daniela Alves, Marília Gomes","doi":"10.1007/s12032-025-03046-z","DOIUrl":"https://doi.org/10.1007/s12032-025-03046-z","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the Western World, with 70% of patients asymptomatic at diagnosis. Treatment initiation follows specific criteria, including evidence of active disease. Recent advancements in Bruton's tyrosine kinase (BTK) inhibitors like acalabrutinib and zanubrutinib offer improved efficacy and safety profiles, impacting treatment choice for all patients namely elderly patients with comorbidities. In this opinion paper, a panel of experienced hematologists sought to establish criteria for selecting therapy in CLL and examine how the introduction of second-generation BTK inhibitors will influence these criteria. Experts recommend prioritizing criteria for CLL treatment selection: cytogenetics, comorbidities, age, socioeconomic factors, and patient preferences. Assessing IGHV mutational status, del(17p), and TP53 mutation is crucial for predicting treatment response, with repeat assessments for the latter before each retreatment. Comorbidities and patient well-being, including literacy, adherence, and living conditions, should be considered. Age alone should not limit treatment options; a holistic approach is needed, including geriatric evaluation. Patient involvement in treatment decisions is vital, considering treatment comprehension, toxicity, and individual preferences. New-generation BTK inhibitors offer improved efficacy and lower toxicity, particularly beneficial for patients with multiple comorbidities, including cardiovascular conditions. In conclusion, in the era of targeted therapies, treating elderly and multimorbid CLL patients requires balancing safety and efficacy, considering quality of life and life expectancy. Targeted therapy is preferred for most patients, with geriatric assessment pivotal for treatment decisions. Second-generation drugs aim to improve outcomes both in efficacy and safety, advocating for a patient-centered approach in clinical studies.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"493"},"PeriodicalIF":3.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on 'The mechanism of ncRNA in trastuzumab resistance in HER2-positive tumors'.","authors":"Kadri Altundag","doi":"10.1007/s12032-025-03064-x","DOIUrl":"https://doi.org/10.1007/s12032-025-03064-x","url":null,"abstract":"","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"491"},"PeriodicalIF":3.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro cytotoxic and pro-apoptotic effects of Chaetoceros socialis ethanolic extract on prostate (LNCap) and glioblastoma (U-87 MG) cells via modulation of AKT/PTEN, mTOR, BAX/BCL2, and Caspase pathways.","authors":"Abbas Asoudeh-Fard, Hossein Hosseinzadeh Jahromi, Zahra Zare, Abbas Fazlinia, Mohammad Bagher Nazari, Asghar Parsaei","doi":"10.1007/s12032-025-03034-3","DOIUrl":"https://doi.org/10.1007/s12032-025-03034-3","url":null,"abstract":"<p><p>Cancer remains a leading cause of mortality worldwide, with prostate cancer and glioblastoma being particularly challenging to treat due to dysregulated apoptotic and survival pathways. Natural marine products, such as extracts from the diatom Chaetoceros socialis, may offer promising in vitro cytotoxic and pro-apoptotic activities that justify further mechanistic and in vivo investigation towards therapeutic development. This study investigates the anticancer effects of ethanolic extract of Chaetoceros socialis on human prostate cancer (LNCap) and glioblastoma (U-87 MG) cell lines by targeting key apoptotic and survival signaling pathways. Cell viability was assessed using MTT assay following treatment with varying concentrations of the extract. Apoptosis induction was evaluated by Annexin V-FITC/PI staining and flow cytometry. Gene expression levels of apoptosis and survival-related markers, including CASP3, CASP8, CASP9, BAX, BCL2, AKT, PTEN, mTOR, FAS, P53, and P21, were quantified via real-time PCR. Normal HUVEC cells were used to evaluate extract selectivity. Chaetoceros socialis extract significantly reduced viability of LNCap and U-87 MG cells in a dose-dependent manner, with minimal toxicity to normal HUVECs. Apoptosis assays revealed increased early and late apoptotic cell populations in treated cancer cells. Gene expression analysis demonstrated upregulation of pro-apoptotic genes (BAX, CASP3, CASP8, CASP9) and tumor suppressors (PTEN, P53, P21), along with downregulation of survival-promoting genes (AKT, mTOR, BCL2). The ethanolic extract of Chaetoceros socialis exerts selective cytotoxic and pro-apoptotic effects on prostate (LNCap) and glioblastoma (U-87 MG) cell lines in vitro by modulating apoptotic and survival pathways. These results indicate an in vitro anticancer potential that requires further protein-level mechanistic validation and in vivo studies to confirm therapeutic relevance.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"488"},"PeriodicalIF":3.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging roles and therapeutic potential of non-coding RNA in osteosarcoma: a review.","authors":"Srijita Chatterjee, Prasenjit Adhikary, Purna Chandra Pal","doi":"10.1007/s12032-025-03036-1","DOIUrl":"https://doi.org/10.1007/s12032-025-03036-1","url":null,"abstract":"<p><p>Osteosarcoma (OS) is recognized as the most prevalent primary malignant bone tumor, characterized by rapid progression, early metastasis, limited efficacy of conventional chemotherapy or radiotherapy, and unfavorable clinical outcomes. Recent studies have highlighted the critical role of non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, and circular RNAs, in the regulation of osteosarcoma biology. The altered expression of these molecules significantly influences tumor cell proliferation, migration, apoptosis, and angiogenesis. Moreover, their dysregulation has been associated with drug resistance and disease recurrence. Given these attributes, ncRNAs are emerging as potential biomarkers for both diagnosis and prognosis, as well as promising therapeutic targets. A more profound understanding of their molecular mechanisms may aid in the development of more effective and personalized strategies for managing osteosarcoma.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"490"},"PeriodicalIF":3.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dual role of PCDH9 in tumors, neurological and developmental diseases.","authors":"Haohan Li, Yuan Wang, Xinghe Tong, Yanlong Yang, Yinsong Tian, Jie Jia, Tao He, Rui Liu, Xudong Yang, Xiaobo Chen","doi":"10.1007/s12032-025-03056-x","DOIUrl":"https://doi.org/10.1007/s12032-025-03056-x","url":null,"abstract":"<p><p>Protocadherin 9 (PCDH9), a member of the δ1-protocadherin family, plays a crucial role in regulating cell polarity, tumor suppression, and neurodevelopment. This is achieved through its dual functions of extracellular calcium-dependent adhesion and intracellular signal transduction. In the context of tumors, PCDH9 inhibits epithelial-mesenchymal transition and cell cycle progression in various cancer types, such as liver cancer and glioma, via the GSK-3β/Snail1 axis. However, in Group 4 medulloblastoma, functionally acquired mutations in PCDH9 drive cancer development through the non-classical Wnt pathway. The expression of PCDH9 is tightly regulated by microRNAs (e.g., miR-589-3p) and epigenetic silencing mechanisms. Within the nervous system, PCDH9 deficiency gives rise to abnormal autistic behaviors, disruptions in hippocampal migration, and abnormal cerebrospinal fluid circulation. Its potential for clinical translation is evident in several areas, including the use of methylation as a prognostic marker, β-eucalyptol-mediated therapy to restore PCDH9, and strategies that target the piRNA-PI3K/AKT axis. Looking ahead, it is essential to conduct in-depth analyses of its evolutionary adaptability and formulate strategies targeting the adherent-signal interface.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"489"},"PeriodicalIF":3.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}