Medical Oncology最新文献

{"title":"A novel naphthoquinone compound triggers DNA damage-induced apoptosis on cholangiocarcinoma through upregulation of BAX.","authors":"Gizem Bulut, Merve Kayis, Dilan Gezer, Zeliha Gokmen, Zelal Adiguzel, Chiara Raggi, Engin Ulukaya","doi":"10.1007/s12032-025-02927-7","DOIUrl":"10.1007/s12032-025-02927-7","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA), a devastating malignancy originating from the bile ducts, is of significant clinical importance due to its rising incidence and poor prognosis. Quinones as being naturally occurring compounds and their frequent utility in anticancer drug development studies seem to be potential sources for the discovery of new chemotherapeutics. In this study, a synthetic naphthoquinone derivative newly synthesized and previously published by our group, named as MK13, has been tested against intrahepatic-CCA (iCCA) cell lines (CCLP1 and HUCCT1). Cell viability was measured with the MTT assay at the doses of 1.56-50 µM for 48 h treatment. Cell death was showed both morphologically with fluorescent double staining and biochemically with flow cytometry analysis of phosphatidylserine translocation. Oxidative stress and DNA damage were also measured with flow cytometry and gene expressions were interpreted via qPCR analysis. MK13 resulted in a strong reduction (about 80%) in viability, especially against CCLP1 cells when compared with doxorubicin. Cell death resulted from apoptosis was shown to be triggered by severe DNA damage that is independent of oxidative stress. Apoptosis was confirmed at molecular level with the upregulation of BAX, a pro-apoptotic BH-3 only protein, and DR5, a cell surface death receptor. MK13 seems to be a promising anticancer compound against iCCA and deserves further attention for in vivo proof-of-concept studies.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"354"},"PeriodicalIF":3.5,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675253","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":"Harnessing the oral-systemic axis: A novel frontier in cancer management.","authors":"Anjana Parmar, Palwinder Kaur, Mandeep Kaur, Palakurthi Yanadaiah","doi":"10.1007/s12032-025-02921-z","DOIUrl":"10.1007/s12032-025-02921-z","url":null,"abstract":"<p><p>The human body harbors numerous microorganisms, including bacteria, fungi, viruses, and bacteriophages, which are primarily found in the oral cavity and are considered the largest microbiological reservoir. The oral microbiota has a profound influence on the human body and health. An imbalance between the bacteria and their hosts may cause local oral and dental difficulties. The recent research has indeed underscored the significant role of oral microbial dysbiosis in the development of various systemic and long-term diseases, potentially culminating in cancer by triggering oncogenic processes in the body. The analogy of activated pathways depends on the involvement of a specific subset of microbial species or consortia within the oral cavity. This review explains the pivotal role of oral microbial dysbiosis in cancer pathogenesis. It also specifies the role of specific oral pathogens and associated mechanisms through which dysbiotic oral microbiota contribute to oncogenic processes. As a rational and innovative approach, the review features various phytotherapeutics that are found to be active against pathogenic oral microbes and also show activity against systemic cancers. This review aims to emphasize the oral-systemic axis by highlighting phytotherapies known for their cancer management properties, which have shown activity against oral microbes and are linked to the pathogenesis of the respective cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"348"},"PeriodicalIF":3.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667934","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":"Symplocamide A as marine-derived proteasome inhibitor: a promising scaffold for targeted cancer therapy.","authors":"Humeyra Cavdar Dincturk, Aysenur Betul Bilgin, Deniz Günal Köroğlu, Celale Kirkin Gozukirmizi, Gulay Ozkan, Esra Capanoglu, William N Setzer, Dietrich Büsselberg, Daniela Calina, Javad Sharifi-Rad","doi":"10.1007/s12032-025-02870-7","DOIUrl":"10.1007/s12032-025-02870-7","url":null,"abstract":"<p><p>Symplocamide A (Sym A), a 3-amino-6-hydroxy-2-piperidone (Ahp)-containing cyclodepsipeptide derived from the marine cyanobacterium Symploca sp., has emerged as a promising candidate in anticancer research. With potent serine protease and proteasome inhibition, Sym A has demonstrated nanomolar cytotoxicity across several cancer cell lines, including lung and neuroblastoma models. This review critically assesses the anti-cancer mechanisms, pharmacokinetic properties, synthetic approaches, and translational limitations of Symplocamide A, highlighting its potential and challenges as a therapeutic agent in oncology. A systematic literature review was performed using PubMed, Scopus, Web of Science, Google Scholar, and the TRIP database, incorporating studies published until March 2025. Articles were selected based on predefined inclusion criteria focusing on Sym A's anticancer activity, mechanisms of action, bioavailability, synthesis, and toxicity profiles. Sym A exhibits selective cytotoxicity toward various cancer cell lines, notably inhibiting chymotrypsin with over 200-fold greater potency than trypsin. Structural analysis underscores the role of Ahp and brominated tyrosine residues in target affinity and stability. Pharmacokinetic modeling indicates favorable intestinal absorption and drug-likeness, although brain penetration is limited. Synthetic production remains inefficient, with low overall yield. No in vivo or clinical studies have yet been reported. Toxicological concerns are heightened by its structural similarity to cyanotoxins, necessitating cautious evaluation. Symplocamide A demonstrates high preclinical anticancer potential through protease inhibition and favorable bioavailability traits. Nonetheless, its clinical translation is hindered by synthesis challenges, the absence of in vivo validation, and undefined toxicity. Further studies are warranted to evaluate its therapeutic window, optimize synthetic accessibility, and assess safety in vivo.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"351"},"PeriodicalIF":3.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667959","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":"Breaking the oncogenic link: BCL10-MALT1 disruption as a precision strike against NF-κB-driven lymphomas.","authors":"Emadeldin M Kamel, Sally Mostafa Khadrawy, Ahmed A Allam, Noha A Ahmed, Faris F Aba Alkhayl, Al Mokhtar Lamsabhi","doi":"10.1007/s12032-025-02897-w","DOIUrl":"10.1007/s12032-025-02897-w","url":null,"abstract":"<p><p>The CARMA1-BCL10-MALT1 (CBM) complex plays a pivotal role in mediating antigen receptor-induced activation of NF-κB, a pathway critical for lymphocyte survival and proliferation. In aggressive lymphoid malignancies such as activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL), oncogenic mutations drive constitutive CBM complex activation, leading to chronic NF-κB signaling and treatment resistance. Traditional therapeutic approaches have focused on inhibiting MALT1's protease activity; however, these strategies incompletely suppress CBM-driven signaling and may provoke immune-related toxicities by selectively impairing regulatory T cell function. Recent insights into the structural basis of CBM assembly have identified the BCL10-MALT1 interaction, particularly the hydrophobic groove between MALT1's Ig1-Ig2 domains, as a critical therapeutic target. Small-molecule inhibitors such as M1i-124 have demonstrated the ability to disrupt this interaction, leading to dual inhibition of MALT1's scaffolding and protease activities, destabilization of the CBM complex, and selective toxicity toward ABC-DLBCL cells. Preclinical studies show promising efficacy with broad suppression of NF-κB signaling and cytokine production while minimizing off-target effects. This review highlights the biological rationale, preclinical progress, and future directions for targeting the BCL10-MALT1 interface, outlining a transformative strategy for precision therapy in lymphoma and other CBM-dependent diseases.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"350"},"PeriodicalIF":3.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667932","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 metabolic significance of ATP-citrate lyase in cancer: insights into glutamine-fuelled citrate biosynthesis and tumour progression.","authors":"Mohammed Bader, Omar Galy, Mohamed Babiker, Loai Eletr, Mustafa Saeed, Obai Suliman, Muzamil Mahdi Abdel Hamid","doi":"10.1007/s12032-025-02909-9","DOIUrl":"10.1007/s12032-025-02909-9","url":null,"abstract":"<p><p>ATP-citrate lyase (ACLY) is a major metabolic enzyme involved in the citrate to acetyl-CoA conversion, connecting glycolysis with lipid biosynthesis. More evidence has been given for its cancer metabolic role, but its patterns of expression and prognostic value in various cancers remain unclear, particularly in the process of cancer metabolic reprogramming, a feature of cancer progression and drug resistance. We performed a pan-cancer analysis of ACLY expression in six tumour types, bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and liver hepatocellular carcinoma (LIHC), using public databases like TIMER, GEPIA, UALCAN, and cBioPortal. GEPIA and UALCAN were utilized for evaluating prognostic significance, and GEO datasets for external validation. ACLY was consistently overexpressed in reprogrammed cancers (BLCA, BRCA, KIRC, KIRP, and LIHC) (P < 0.05 to P < 0.001) but appreciably downregulated in KICH, a metabolically quiescent cancer. ACLY overexpression was associated with poor prognosis in LIHC and KICH (P = 0.011 and P = 0.0081, respectively) but surprisingly associated with better survival in KIRC (P < 0.0001). Genomic alterations in ACLY were rare (< 4%) across all cancers. The findings were validated by multiple GEO datasets: GSE41804 (LIHC), GSE 3167 (BLCA), GSE 22820 (BRCA), GSE 53757 (KIRC), GSE15641 (KIRP), and GSE15641 (KICH). Conclusion: ACLY expression agrees with the metabolic phenotype of most tumours and has different prognostic implications. Overexpression in metabolically active cancers and association with poor outcomes, namely in LIHC, emphasizes its potential for therapeutic targeting as a tumour metabolic status biomarker. Downregulation in KICH, on the other hand, agrees with evidence of metabolic stability in certain cancers. These findings might be used in the direction of metabolism-based therapeutic approaches and risk stratification in oncology.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"349"},"PeriodicalIF":3.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667961","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":"Advances in nanotechnology for colorectal cancer: a smart targeting and theranostics approach.","authors":"Sanam Priya Sahoo, Sasmita Samal, Roja Sahu, Biswajeet Acharya","doi":"10.1007/s12032-025-02910-2","DOIUrl":"10.1007/s12032-025-02910-2","url":null,"abstract":"<p><p>Colorectal cancer remains one of the most common and deadly malignancies globally, with high mortality rates, particularly in advanced stages. Conventional therapies such as surgery, chemotherapy, and radiotherapy, though beneficial, often suffer from drawbacks including systemic toxicity, multidrug resistance, and poor tumor selectivity. Recent progress in nanotechnology has introduced innovative theranostic strategies that integrate diagnosis and treatment using nanoparticle-based platforms. These nanocarriers can be tailored for both passive and active tumor targeting, as well as stimuli-responsive drug release (e.g., pH, redox, and enzymatic triggers), and provide real-time imaging guidance. Novel approaches, such as the use of Fe₃O₄-based photothermal nanoparticles to induce ferroptosis and immunogenic cell death, or polyphenol-loaded nanoparticles to enhance biocompatibility and therapeutic efficacy, have demonstrated significant potential in colorectal cancer models. Additionally, hydrogels and biopolymer-based systems offer controlled, localized delivery, reducing systemic exposure and side effects. Imaging-assisted therapies, such as MRI-guided photothermal therapy, further refine precision treatment. However, challenges such as tumor heterogeneity, nanoparticle clearance, biological barrier penetration, and clinical scalability remain to be addressed. This review discusses the latest advancements in nanoparticle-mediated colorectal cancer diagnosis and therapy, while also outlining key translational barriers and future directions toward clinically viable nanomedicine strategies.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"346"},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659615","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":"Salvianolic acid B in cancer therapy: pharmacokinetic profile, anticancer mechanisms and translational potential.","authors":"Warren Chanda, Petty M Miyanda, Kingsley Kamvuma, Zainab M Almarhoon, Javad Sharifi-Rad, William N Setzer, Daniela Calina","doi":"10.1007/s12032-025-02892-1","DOIUrl":"10.1007/s12032-025-02892-1","url":null,"abstract":"<p><p>Salvianolic acid B (SalB) is a bioactive compound derived from the root of Salvia miltiorrhiza, a traditional Chinese medicinal herb. Over the years, SalB has gained considerable attention for its potential anticancer properties, but there have not been many clinical trials to commercialize it for usage in people. Therefore, this study provides a broad overview of the state of knowledge regarding the anticancer properties of SalB and focused on the route of administration, pharmacokinetic parameters, type of cancer, study model, drug concentrations, involved signaling pathways, safety and toxicity, efficacy, and mechanisms of action. Numerous in vitro and in vivo studies have demonstrated that SalB exhibits promising anticancer effects against various types of cancers because of its ability to inhibit cancer cell proliferation, induce cell cycle arrest, and promote apoptosis in cancer cells. Additionally, SalB can suppress tumor angiogenesis, invasion, and metastasis, thus inhibiting cancer progression. These underlying mechanisms are multifaceted. SalB exerts its effects through modulation of various signaling pathways among which include inhibition of nuclear factor kappa B and mitogen-activated protein kinase pathways, which are involved in cancer cell survival and proliferation. Moreover, SalB has shown synergistic effects with conventional chemotherapeutic agents, enhancing their efficacy while reducing their side effects. This has significant implications for combination therapy approaches in cancer treatment. Therefore, SalB demonstrates promising anticancer properties through its ability to inhibit cancer cell proliferation, induce apoptosis, inhibit angiogenesis and metastasis, and modulate various signaling pathways. Further preclinical and clinical studies are warranted to fully elucidate its mechanisms of action and assess its potential as a therapeutic agent for various cancers.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"347"},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659617","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":"Sinapic acid induces cytoplasmic stress granule formation, ER stress and apoptosis mediated anticancer activity in human endometrial cancer cell lines.","authors":"Sedef Akçaalan, Fatma Seçer Çelik, Hatice Oruç Demirbağ, Canan Eroğlu Güneş, Ercan Kurar","doi":"10.1007/s12032-025-02926-8","DOIUrl":"10.1007/s12032-025-02926-8","url":null,"abstract":"<p><p>This study aimed to examine the impact of molecular mechanisms in endometrial cancer cell lines (Ishikawa and HEC-1-B) treated with sinapic acid (SA), which may have effect on regulation of genes in various processes including unfolded protein response and apoptosis. The impact of SA on cell viability was assessed through the XTT assay. Expressions of genes in apoptosis and endoplasmic reticulum (ER) stress pathways were evaluated using qPCR and western blot analyses. Effects of SA on colony formation and ER structure were determined using colony assay and transmission electron microscopy (TEM) visualization. The results showed a significant upregulated expression of CASP7, CASP8, CASP9, P53, ATF6, Eif2a, HSP47, IRE1 and PERK genes in Ishikawa cells. In HEC-1-B cells, expression of CASP3, CASP8, CYCS, FAS, P53, ATF6, CALR, CHOP, Eif2a, GRP78, HSP47, IRE1 and XBP1 genes were significantly increased, however FADD levels were decreased. Western blot analysis illustrated that comparing to the control CASP9 and CASP8 protein levels were increased in Ishikawa and in HEC-1-B cell lines, respectively. SA significantly suppressed colony formation capacities in both cell lines. TEM analyses also demonstrated that SA induced cytoplasmic stress granule formation in both cell lines. Therefore, this study suggested that SA can be a potential anticancer therapeutic agent for endometrial cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"345"},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659618","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":"Nostoc commune-derived scytonemin induced mitochondrial cell death in leukemia models.","authors":"Simona Zilakova, Martina Gavurova, Dominika Sebova, Michal Goga, Martin Backor, Viktoria Medvecova, Dajana Kecsey, Martin Kello","doi":"10.1007/s12032-025-02890-3","DOIUrl":"10.1007/s12032-025-02890-3","url":null,"abstract":"<p><p>Cyanobacteria have long attracted scientific interest through their potential application in the development of new therapeutic approaches, particularly those related to the treatment of cancer. In this study, the antiproliferative effects of Nostoc commune extract (NOS) and the cyanobacterial compound scytonemin (SCY) were evaluated against a variety of in vitro cancer models, including cervix, colon, breast, lung, and leukemia cell lines, using resazurin assays. Both of the studied compounds were found to have inhibited metabolic activity in a dose-dependent manner, with IC₅₀ values ranging from 60.5 to 462.0 µM for SCY and 157.0 to 740.3 µM for NOS. SCY displayed higher levels of inhibitory activity than NOS against all of the tested cancer models, but was particularly effective against HL-60 and Jurkat leukemia cells, with IC₅₀ values recorded as 60.5 µM and 88.2 µM, respectively. However in contrast, the two compounds exhibited significantly lower levels of inhibition against non-cancerous MCF-10A and BJ-5ta cells. Flow cytometry studies of leukemia cells treated with SCY revealed that the compound had effectively inhibited cell proliferation over prolonged periods; HL-60 cells displayed G1 phase arrest which lasted for 48 h, while an accumulated G0/G1 sub-population was detected in Jurkat cells, as indicator of apoptosis. Further analysis of cells treated with SCY observed reduced levels of Rb protein and an increase in p21 expression in both HL-60 and Jurkat cell lines. Apoptotic markers such as phosphatidylserine externalization were observed, and mitochondrial dysfunction characterized by the dissipation of mitochondrial membrane potential was also detected. SCY activated the mitochondrial apoptotic pathway, inducing cytochrome c release and subsequent caspase-9, -3, and -7 activation. Finally, PARP cleavage, a typical marker of apoptosis, was identified in both leukemia cell lines following treatment with SCY. The findings suggest that SCY induces apoptosis in leukemia cells through the activation of the mitochondrial pathway, highlighting its potential for development as a future anti-cancer agent.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"341"},"PeriodicalIF":3.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649873","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":"Letter to the editor.","authors":"Beverley de Valois, Teresa Young","doi":"10.1007/s12032-025-02885-0","DOIUrl":"10.1007/s12032-025-02885-0","url":null,"abstract":"","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 8","pages":"342"},"PeriodicalIF":3.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649872","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}