Medical Oncology最新文献

{"title":"Water-based propolis enhances 5-fluorouracil drug efficiency in gastric and colorectal cancer cells through cell stress response, anti-migratory, and apoptotic effects regardless of p53 status.","authors":"Muhsin Attila Göksoy, Yunus Aksüt, Aslıhan Şengelen, Nazlı Arda","doi":"10.1007/s12032-025-03023-6","DOIUrl":"10.1007/s12032-025-03023-6","url":null,"abstract":"<p><p>Digestive system tumors, including gastric and colorectal cancers, have notable global incidence and mortality rates. While 5-Fluorouracil (5-FU) is widely used in treating gastrointestinal (GI) cancers, resistance often limits its effectiveness. Recent research has focused on the potential of natural products, such as propolis, a resin produced by honeybees, as adjuncts in cancer therapy. This study examined whether water-based propolis (WBP) could enhance the therapeutic effects of 5-FU on AGS (p53-wild-type) and Caco-2 (p53-null) cancer cell lines, aiming to propose a new combined treatment strategy. The findings demonstrated that WBP and 5-FU exhibited dose- and time-dependent cytotoxicity, with WBP increasing the therapeutic efficiency of 5-FU by reducing its half-maximal inhibitory concentration in both cancer cell lines, and reducing 5-FU toxicity in non-cancerous cells. Notably, cancer cells expressing p53 showed greater sensitivity to 5-FU; however, WBP demonstrated similar effects in both cell lines. The combined therapy of WBP (100 µg/mL for 48-h) and 5-FU (10 µg/mL for 48-h) with synergistic effects significantly reduced cell proliferation and motility. Moreover, combined treatments caused increased reactive oxygen species production, collapse of mitochondrial membrane potential, endoplasmic reticulum stress, and autophagy, thus leading to cell cycle arrest and apoptosis compared to individual treatments and controls, regardless of p53 expression in both cancer cells. These findings suggest that WBP, a natural product, could supplement 5-FU chemotherapy by enhancing its antitumor effectiveness, warranting further investigation for treating GI cancers.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"449"},"PeriodicalIF":3.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960477","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 landscape of cyclin-dependent kinase 4/6 inhibitors in solid malignancies: emphasis on immunotherapy combinatorial strategies.","authors":"Sara A Hussein, Ahmed H Saadawy, Eman Badr, Maha R A Abdollah, Neamtullah Wael, Rasha M Allam, Ahmed M Al-Abd, Ana Maria Roncero Sanchez, Mai F Tolba","doi":"10.1007/s12032-025-02996-8","DOIUrl":"10.1007/s12032-025-02996-8","url":null,"abstract":"<p><p>Given the pivotal role of CDK4/6 deregulation in the pathogenesis of various malignancies, CDK4/6 inhibitors have been incorporated into cancer treatment protocols. Beyond their antiproliferative effects, these inhibitors exhibit prominent immunomodulatory properties. Preclinical data indicated that CDK4/6 inhibitors enhance the tumor cell antigen presentation capacity and restrict the proliferation of immunosuppressive regulatory T-cells. Furthermore, studies showed that CDK4/6 inhibitors could enhance the development of memory T-cell in vivo in melanoma mouse models and in the clinical setting in breast cancer (BC) patients. In silico analysis identified 225 protein targets for CDK4/6 inhibitors involved in 57 immune-related pathways which further supported the immune-modulatory potential of these inhibitors in innate immunity, cytokine signaling, and adaptive immunity. Furthermore, 24 targets exhibited significantly higher protein expression in immune cell types compared to non-immune cell types, as indicated by data from the Human Protein Atlas. The favorable modulation of T-cell immunity by CDK4/6 inhibitors could complement the antitumor effect of immunotherapies, such as immune checkpoint inhibitors (ICIs), which hamper PD-1 /PD-L1 signaling and result in the reactivation of the antitumor T-cell response. Herein, we explore the clinical portfolio of CDK4/6 inhibitors across various solid malignancies, with emphasis on emerging combinations with ICIs.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"447"},"PeriodicalIF":3.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune profiling in oncology: bridging the gap between technology and treatment.","authors":"Nanthini Ravi, Gee Jun Tye, Satvinder Singh Dhaliwal, Muhamad Yusri Musa, Matthew Tze Jian Wong, Ngit Shin Lai","doi":"10.1007/s12032-025-03002-x","DOIUrl":"10.1007/s12032-025-03002-x","url":null,"abstract":"<p><p>Immune profiling has become a transformative tool in oncology, offering comprehensive information on tumor immune interactions and facilitating precision medicine. Recent advances such as mass cytometry (CyTOF), single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and liquid biopsy have greatly enhanced our ability to characterize immune heterogeneity and predict treatment responses. These innovations support the identification of new biomarkers, therapeutic targets, and resistance mechanisms, refining patient stratification and clinical results. Additionally, artificial intelligence (AI) driven models are now being employed to integrate multi-omics datasets and create predictive insights, thereby linking the gap between research and clinical decision-making. This review studies the evolution of immune profiling technologies, their integration into real-world oncology practice, and the associated technical and analytical challenges, including sample variability, data harmonization, and multi-omics integration. Although challenges such as cost, throughput, and standardization persist, the merging of advanced technologies, bioinformatics, and clinical frameworks promises to reshape cancer diagnosis, therapy selection, and disease monitoring through personalized and data-driven strategies.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"446"},"PeriodicalIF":3.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chrysin mitigates therapy-induced senescence in breast cancer via cGAS-STING pathway inhibition.","authors":"Rezina Billimoria, Purvi Bhatt","doi":"10.1007/s12032-025-02993-x","DOIUrl":"10.1007/s12032-025-02993-x","url":null,"abstract":"<p><p>Breast cancer continues to be a leading cause of cancer-related deaths among women globally, with cellular senescence having a complex role in its progression. Senescence is linked to chronic inflammation via the senescence-associated secretory phenotype (SASP). The cyclic guanosine monophosphate-adenosine monophosphate (cGMP-AMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway, activated by cytoplasmic chromatin fragments (CCFs) marked by histone modifications (H3K27me3 and H3K9me3), is crucial for SASP production. This study investigates the potential of a natural flavonoid, Chrysin, as a senomorphic agent that targets these CCF markers to reduce inflammation in senescent breast cancer cells. We induced senescence in MDA-MB-231 and MCF-7 cells using doxorubicin and analyzed the expression levels of inflammatory cytokines IL-6 and IL-8 after treatment with various concentrations of Chrysin through qRT-PCR. Western blotting and immunofluorescence revealed significantly reduced CCF markers H3K9me3 and H3K27me3, along with decreased STING phosphorylation. Notably, Chrysin did not change the expression of senescent markers p16 or p21. Additionally, Chrysin effectively inhibited SASP-driven breast cancer cell invasion and colony formation, highlighting its potential as both an anti-inflammatory agent and a senomorphic drug. Chrysin notably decreases H3K9me3 and H3K27me3-marked CCF levels, suppressing cGAS-STING pathway activation and reducing IL-6 and IL-8 levels. Our findings indicate that Chrysin represents a promising therapeutic strategy, targeting the epigenetic landscape of CCFs and modulating the SASP to mitigate the harmful effects of senescent cells in the tumor microenvironment.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"445"},"PeriodicalIF":3.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960313","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":"Female and male hormonal-dependent malignancies: the role of long non-coding RNAs.","authors":"Yahia Elgharib, Karim Medhat, Fayrouz Fouad, Faten Elgharib, Ekram Saleh","doi":"10.1007/s12032-025-03001-y","DOIUrl":"10.1007/s12032-025-03001-y","url":null,"abstract":"<p><p>Since their discovery, long non-coding RNAs (lncRNAs) have emerged as critical regulators of diverse biological processes across various tissues. Their dysregulation has been strongly linked to cancer progression. LncRNAs influence key aspects of tumor biology, including cell proliferation, invasion, metastasis, apoptosis, and therapeutic resistance, acting either as oncogenes or tumor suppressors. In hormone-dependent malignancies such as breast and prostate cancers, lncRNAs play pivotal roles by modulating hormone signaling pathways and regulating the expression and activity of hormone receptors, including estrogen (ER), progesterone (PR), and androgen receptors (AR). Despite increasing evidence of their involvement, many of these lncRNAs remain poorly characterized, and their potential as diagnostic markers or therapeutic targets is still under investigation.This review aims to critically synthesize recent advances in the understanding of lncRNAs in hormone-dependent cancers, with a focus on their oncogenic and tumor-suppressive roles, involvement in drug resistance, and clinical relevance. By highlighting both established findings and areas requiring further research, we seek to provide a comprehensive and insightful overview that can inform future therapeutic strategies and translational applications.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"444"},"PeriodicalIF":3.5,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960405","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":"Drug repurposing in oncology: a path beyond the bottleneck.","authors":"Neha Sajwani, G P Suchitha, T S Keshava Prasad, Shobha Dagamajalu","doi":"10.1007/s12032-025-02994-w","DOIUrl":"10.1007/s12032-025-02994-w","url":null,"abstract":"<p><p>Cancer is a major worldwide health burden, with rising incidence and mortality rates highlighting the critical need for more effective and accessible treatment alternatives. Conventional drug development is often hindered by long timelines, high prices, and significant failure rates, making it unable to fulfil the rapidly increasing therapeutic demands. In this context, drug repurposing, identifying new therapeutic applications for existing medications with proven safety profiles, has emerged as a potential and cost-effective alternative to traditional drug discovery. Although numerous studies have explored the anticancer prospects of repurposed drugs, there exists a lack of systematic and cumulative knowledge regarding the varied therapeutic classes of interest for oncological purposes. This is critical as a deeper understanding of mechanisms, discovery methods, and translational challenges would significantly boost the clinical use of repurposed drugs. This review provides an overview of ongoing drug repurposing activity in anticancer therapy, targeting diverse therapeutic groups like cardiovascular, antibacterial, antiviral, anti-inflammatory, antidepressant, and antipsychotic drugs. It highlights approved drugs such as metformin, which acts on the AMPK/mTOR pathway to suppress cancer cell proliferation, thalidomide, which is approved for use in multiple myeloma because it has antiangiogenic and immunomodulatory effects, and propranolol, which inhibits β-adrenergic signaling, suppressing VEGF-induced angiogenesis in breast and ovarian cancer. Drugs such as statins, sertraline, and ribavirin target different pathways like HMG-CoA reductase, autophagy regulation, and eIF4E inhibition, respectively. Regulatory pathways like the FDA's 505(b)(2) process, orphan drug status, and approaches for overcoming intellectual property issues are discussed. Through the convergence of mechanistic insight and clinical and regulatory perspectives, drug repurposing is a pragmatic approach to expand oncologic therapeutic options and promote bench-to-bedside translation. It also addresses major issues within this context, including tumor heterogeneity, regulatory barriers, and translational gaps, restricting clinical acceptance of repurposed drugs. Through the examination of these aspects, the potential of drug repurposing as an innovative strategy in oncology is shown to offer efficient, cost-effective, and rapidly deployable therapy. These options can enhance patient outcomes and change the future of cancer treatment.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"443"},"PeriodicalIF":3.5,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960371","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":"Gold nanoparticles capped with inclusion complex for the delivery of Chrysin in triple-negative breast cancer.","authors":"Kamini Velhal, Parvindar Sah, Rajesh Raut, Smitali Patil, Sagar Barage, Jaya Lakkakula, Imran Uddin","doi":"10.1007/s12032-025-03011-w","DOIUrl":"10.1007/s12032-025-03011-w","url":null,"abstract":"<p><p>Chrysin (CHR), a naturally occurring flavonoid with promising anticancer potential, suffers from poor water solubility, limiting its therapeutic applications. To address this, β-Cyclodextrin (β-CD) inclusion complexes (ICs) of CHR were synthesized via the freeze-drying method at varying molar ratios (1:1, 1:2, 1:3, 1:4), with the 1:4 ratio exhibiting the highest entrapment efficiency (95.23%) and selected for further study. These ICs were then functionalized onto gold nanoparticles (AuNPs) to develop CHR-β-CD-AuNPs, enhancing drug delivery and stability. Characterization by UV-Vis, FTIR, NMR, NTA, and TEM confirmed successful encapsulation, hydrogen bonding, and spherical morphology with an average particle size of ~ 43 nm. Molecular docking supported strong interactions between CHR and β-CD. In vitro studies against human triple-negative breast cancer (MDA-MB-231) cells demonstrated that CHR-β-CD-AuNPs exhibited potent cytotoxicity with an IC₅₀ of 22.17 ± 1.24 mg/L, significantly lower than CHR/β-CD ICs (IC₅₀: 22.84 ± 1.00 mg/L) and free CHR (IC₅₀ > 100 mg/L, p < 0.001). Hoechst and phalloidin staining revealed clear apoptotic features such as nuclear fragmentation and cytoskeletal disruption. Gene expression analysis showed upregulation of Bax and Caspase-3 and downregulation of Bcl-2, confirming apoptosis induction. Furthermore, scratch wound assays demonstrated significant inhibition of cancer cell migration, with wound closure reduced to 8.38 ± 0.74% (IC) and 15.27 ± 1.05% (IC-AuNPs) compared to 74.41 ± 1.22% in untreated controls (p < 0.001). These findings establish that β-CD-based CHR-AuNP nanocarriers substantially improve the solubility, stability, and therapeutic efficacy of CHR, offering a promising nanoformulations strategy for enhanced targeted breast cancer therapy.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"441"},"PeriodicalIF":3.5,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960339","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":"Cabo Verde's cancer crisis: the fastest-rising mortality burden in the world.","authors":"Shree Rath","doi":"10.1007/s12032-025-02995-9","DOIUrl":"10.1007/s12032-025-02995-9","url":null,"abstract":"","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"440"},"PeriodicalIF":3.5,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960346","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":"Response to letter to the editor about \"current evidence on patient precautions for reducing breast cancer-related lymphedema (BCRL) manifestation and progression risks\".","authors":"Julie Hunley, David Doubblestein, Elizabeth Campione","doi":"10.1007/s12032-025-02991-z","DOIUrl":"10.1007/s12032-025-02991-z","url":null,"abstract":"","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"439"},"PeriodicalIF":3.5,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960400","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":"Molecular interplay of ARID1A in gastrointestinal cancers.","authors":"Alina Athar, Ejaj Ahmad, Pinki Bera, Md Abu Nasar, Khalid Imtiyaz, Mohammad Moshahid Alam Rizvi, Sundeep Singh Saluja","doi":"10.1007/s12032-025-03014-7","DOIUrl":"10.1007/s12032-025-03014-7","url":null,"abstract":"<p><p>ARID1A is a subunit of the SWI/SNF chromatin remodeling complex that plays a dual role in cancer biology as a tumor suppressor or an oncogene dependent on the cellular context. It is frequently found to be altered in gastrointestinal (GI) cancers esophageal, gastric, hepatocellular, pancreatic and colorectal carcinomas. With approximate mutation rates of 19-20% in gastric and colorectal cancers and up to 10% across all tumors. ARID1A regulates gene expression, genomic stability, and major oncogenic pathways like PI3K/AKT and YAP/TAZ. Its loss has been associated with poor prognosis, increased tumor aggressiveness and pronounced resistance to treatment. In gastric carcinoma, the lack of ARID1A correlates with enhanced tumor invasiveness, poor survival, and immune checkpoint expression offering therapeutic interventions with PARP inhibitors and advanced immunotherapies. Similarly in colorectal cancer, ARID1A alterations are related to microsatellite instability (MSI), affecting tumor behavior and immune responses. In contrast, hepatocellular carcinoma in the absence of ARID1A promotes angiogenesis and tumor progression, while pancreatic cancer displays its role in epithelial-mesenchymal transition (EMT) and metastasis by YAP/TAZ pathway activation. Moreover, miRNA-mediated regulation of ARID1A modulates tumor progression and provides resistance to treatment, for instance, miR-129-5p and miR-3613-3p have been implicated in prognosis. Alongside genetic and molecular studies, our bioinformatics analyses reveal considerable heterogeneity in ARID1A mutational signatures and expression across GI cancers, underscoring its stage-specific prognostic and therapeutic implications. The coexistence of truncating and missense variants further highlights the need for mechanistic validation, and integrative pathway analysis to identify synthetic lethal targets and improve the therapeutic strategies. Integrating ARID1A into precision oncology is a promising approach for improving the diagnostic, prognostic, and treatment modalities for patients with ARID1A-deficient cancers.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"442"},"PeriodicalIF":3.5,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960374","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}