Medical Oncology最新文献

{"title":"Noncoding RNA (ncRNA)-mediated regulation of TLRs: critical regulator of inflammation in tumor microenvironment.","authors":"Tawfeeq Alghazali, Abdulrahman T Ahmed, Uday Abdul-Reda Hussein, Gaurav Sanghvi, Subasini Uthirapathy, Reem Turki Edan, Madan Lal, Debasish Shit, K Satyam Naidu, Ahmed Khudhair Al-Hamairy","doi":"10.1007/s12032-025-02690-9","DOIUrl":"https://doi.org/10.1007/s12032-025-02690-9","url":null,"abstract":"<p><p>Toll-like receptors (TLRs) are central components of the innate immune system as they recognize molecular patterns associated with pathogens and cellular damage and initiate immune responses using MyD88- and TRIF-dependent pathways. In contrast to being very useful for immune defense, dysregulated TLR signaling may be involved in diseases, such as cancer and autoimmune conditions. In cancer, TLRs create an environment that supports tumorigenesis and growth. In addition to this, a class of multifunctional noncoding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, regulate gene expression without encoding proteins. MiRNAs regulate gene expression in a fine-tuned manner, while lncRNAs and circRNAs do so via diverse mechanisms. Notably, these ncRNAs interact, where lncRNAs and circRNAs function as competing endogenous RNAs and ceRNA, affecting miRNA activity. This interaction has a vital role in cancer pathology, in influencing that of various oncogenes and tumor suppressors in the tumor microenvironment; hence, modulation of ncRNAs could also be a great promising therapeutic approach. In this context, interplay between TLRs and ncRNAs is of paramount importance as they influence various parameters of the tumor microenvironment. TLR signaling works upon the expression of ncRNAs, while ncRNAs work back to regulate TLR signaling in return. An example of this includes miRNA targeting of components of the TLR; lncRNAs induced by TLR signaling possibly would favor tumor progression. Pharmacological interventions directed toward inhibiting these TLR pathways could be the model to halt malignancy by hampering pro-tumor inflammation and boosting immune responses against neoplasms. Hence, the review will highlight the complicated contrast of ncRNAs and TLRs within human cancer. By connecting the mechanisms, the researchers may study more about tumorigenesis and gather up new, innovative notions regarding therapeutic targeting.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"144"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753349","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":"Alternative use of droxidopa for treating cervical cancer: inhibiting transferase, cell cycle signalling, and transport proteins via multitarget docking, DFT, MD simulations, and binding free energy studies.","authors":"Saleh Hussain A Almasabi, Hassan H Almasoudi, Hassan Albargy, Meshal Mansour A Alabbas, Fares Saeed H Al-Mansour","doi":"10.1007/s12032-025-02700-w","DOIUrl":"https://doi.org/10.1007/s12032-025-02700-w","url":null,"abstract":"<p><p>Cervical cancer develops due to the uncontrolled growth of abnormal cells in the cervix, mainly triggered by a persistent infection with high-risk types of human papillomavirus (HPV), a sexually transmitted virus. Factors that increase the risk include having multiple sexual partners, engaging in sexual activity at an early age, smoking, and a compromised immune system. Globally, it ranks as the fourth most prevalent cancer among women, with over 600000 new cases and 340000 deaths each year. The disease disproportionately impacts women in low- and middle-income countries, where access to screening and vaccination is often limited. Drug resistance emerges when cancer cells evade treatment through genetic mutations, altered targets, and efflux pump overexpression. Multitargeted docking identifies compounds interacting with multiple targets where a drug can inhibit crucial pathways, improving efficacy and reducing resistance chances. In this study, we examined Transferase, Cell Cycle Signalling, and Transport Proteins associated with PDB IDs 2WVI, 2B9R, 3VHX, and 3KND. These targets were subjected to multitargeted docking using an FDA-approved drug library. Droxidopa was identified as a multitargeted drug, with docking scores ranging from - 5.99 to - 11.37 kcal/mol and MM/GBSA scores between - 20.13 and - 43.00 kcal/mol. The interaction fingerprints identified the most interacted residues with counts are 4GLN, 4GLU, 3ARG, and 3TRP, and the Pharmacokinetics and DFT analysis favoured the compound's suitability. Furthermore, 5 ns (nanoseconds) WaterMap for hydration sites and 100 ns MD simulation in NPT ensemble at 330 K temperature have resulted in acceptable deviations, fluctuations, and many intermolecular interactions, and binding free energy computations have favoured droxidopa's use against cervical cancer-however, experimental studies are needed before its use including the in-vitro and in-vivo studies.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"143"},"PeriodicalIF":2.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743635","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":"Microenvironment-based immunotherapy in oral cancer: a comprehensive review.","authors":"Hassan Mivehchi, Aisan Eskandari-Yaghbastlo, Mohammaderfan Ghazanfarpour, SeyedMehdi Ziaei, Hassan Mesgari, Farbod Faghihinia, Negin Zokaei Ashtiani, Mohsen Nabi Afjadi","doi":"10.1007/s12032-025-02694-5","DOIUrl":"https://doi.org/10.1007/s12032-025-02694-5","url":null,"abstract":"<p><p>Oral cancer, a prevalent form of head and neck malignancy, accounts for 4% of global cancer cases. The most common type, oral squamous cell carcinoma (OSCC), has a survival rate of about 50%. Even though emerging molecular therapies show promise for managing oral cancer, current treatments like surgery, radiotherapy, and chemotherapy have significant side effects. In addition, the complex tumor microenvironment (TME), involving the extracellular matrix (ECM) and cells like fibroblasts and stromal cells like immune cells, promotes tumor growth and inhibits immune responses, complicating treatment. Nonetheless, immunotherapy is crucial in cancer treatment, especially in oral cancers. Indeed, its effectiveness lies in targeting immune checkpoints such as PD-1 and CTLA-4 inhibitors, as well as monoclonal antibodies like pembrolizumab and cetuximab, adoptive cell transfer methods (including CAR-T cell therapy), cytokine therapy such as IL-2, and tumor vaccines. Thus, these interventions collectively regulate tumor proliferation and metastasis by targeting the TME through autocrine-paracrine signaling pathways. Immunotherapy indeed aims to stimulate the immune system, leveraging both innate and adaptive immunity to counteract cancer cell signals and promote tumor destruction. This review will explore how the TME controls tumor proliferation and metastasis via autocrine-paracrine signaling pathways. It will then detail the effectiveness of immunotherapy in oral cancers, focusing on immune checkpoints, targeted monoclonal antibodies, adoptive cell transfer, cytokine therapy, and tumor vaccines.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"140"},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735772","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":"Targeting TGF-β: a promising strategy for cancer therapy.","authors":"Himani, Charanjit Kaur, Rajesh Kumar, Rakhi Mishra, Gurvinder Singh","doi":"10.1007/s12032-025-02667-8","DOIUrl":"https://doi.org/10.1007/s12032-025-02667-8","url":null,"abstract":"<p><p>Transforming growth factor β (TGF-β) has important role in regulating the cellular processes including cell growth, differentiation, and migration. TGF-β exerts its effect by binding with transcellular membranes and kinases. Our findings demonstrate that TGF- β possess dual role as tumor suppressor and tumor promoter in different stages of cancer. TGF-β emerged as a promising anticancer agent that exhibits the apoptosis by acting on the suppressor of mothers against decapentaplegic (SMAD) and non-SMAD pathways. In this review we are focusing on the different types of TGF- β inhibitors active against skin cancer, breast cancer, colorectal cancer, lung cancer and ovarian cancer. TGF-β inhibitors includes ligand traps, monoclonal antibodies and receptor kinase inhibitors. In recent studies, TGF- β inhibitors have also been used in combination therapies in the treatment of cancer. The TGF-β has important role in vaccine therapy, Chemo and Radio Resistance in Cancer. TGF-β inhibitors present the novel therapeutic approach for the cancer therapy, highlighting the mechanism of action involved, clinical trials, challenges and exploring therapeutic opportunities. This will help to develop the novel TGF-β inhibitors as anticancer agents as well as help to resolve the problem of drug resistance by developing new drugs as anticancer agents.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"142"},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743637","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":"Retraction Note: Long noncoding RNA HULC is a novel biomarker of poor prognosis in patients with pancreatic cancer.","authors":"Wei Peng, Wei Gao, Jifeng Feng","doi":"10.1007/s12032-025-02701-9","DOIUrl":"https://doi.org/10.1007/s12032-025-02701-9","url":null,"abstract":"","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"141"},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735804","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":"Enhancing KRAS G12D inhibitor sensitivity in pancreatic cancer through SHP2/PI3K pathway.","authors":"Man-Wei Hao, Tian-Xing Zhang, Dan Dong, Xin Zhou, Haicheng Gao","doi":"10.1007/s12032-025-02683-8","DOIUrl":"10.1007/s12032-025-02683-8","url":null,"abstract":"<p><p>Pancreatic cancer with the KRAS G12D mutation, found in 40% of cases, is challenging to treat. MRTX1133, a non-covalent KRAS G12D inhibitor, shows therapeutic promise but faces resistance issues. Our study combines MRTX1133 with the SHP2 inhibitor SHP099 or PI3K inhibitor Buparlisib, showing synergistic inhibition of pancreatic cancer cell growth and enhanced apoptosis. These combination therapies could improve clinical outcomes for patients with KRAS G12D  mutation in pancreatic cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"139"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720205","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":"Vitamin D3 and its active form calcitriol suppress erythroleukemia through upregulation of CHAC1 and downregulation of NOTCH1.","authors":"Jiankun Hong, Zhongyou Yang, Jian Gao, Kunlin Yu, Anling Hu, Yi Kuang, Babu Gajendran, Eldad Zacksenhaus, Xiao Xiao, Chunlin Wang, Wuling Liu, Yaacov Ben-David","doi":"10.1007/s12032-025-02695-4","DOIUrl":"10.1007/s12032-025-02695-4","url":null,"abstract":"<p><p>Vitamin D3 (VD3) and its active form calcitriol (Ca) exhibit anti-neoplastic activity against several types of cancer, although the underlying mechanism is not fully understood. Herein, we tested the effects of VD3 and Ca on erythro-leukemogenesis and investigated the underlying mechanism. VD3 and Ca treatment strongly inhibited cancer progression in a mouse model of erythroleukemia induced by the Friend virus. In tissue culture, VD3 and Ca inhibited proliferation of leukemic cell lines. Growth inhibition was associated with induction of G1 phase cell cycle arrest and apoptosis. Transcription of the VD3 receptor, VDR, is strongly induced by Ca, but not VDR. However, leukemia growth suppression by both VD3 and Ca is shown to be independent of VDR. In leukemic cells, both VD3 and Ca induced genes associated with metabolic pathways. Both VD3 and Ca induce the cytosolic glutathione degradase CHAC1 through activation of the ER stress response pathway ATF3/ATF4/CHOP genes. Higher expression of CHAC1 also suppressed the oncogene NOTCH1. Accordingly, knockdown of CHAC1 antagonized the inhibitory effect of VD3 and Ca on leukemic growth leading to higher NOTCH1 expression. Conversely, overexpression of CHAC1 suppressed leukemia cell growth and inhibited the expression of NOTCH1. Additionally, glutathione antagonized leukemia cell suppression induced by VD3 and Ca, demonstrating that this vitamin inhibits the proliferation of leukemic cells via CHAC1. Taken together, our results demonstrated that VD3 and Ca can prolong the survival of leukemia mice and inhibit the proliferation of erythroleukemia cell HEL through CHAC1 or CHAC1-mediated NOTCH1 inhibition.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"138"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720208","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":"Identification of Isovitexin as a novel CYP17A1 inhibitor through virtual screening and evaluation of its anti-cancer effects in MCF-7 breast cancer cells.","authors":"Lathika Shanmugam, Priyadharshini Kaliyamoorthy, Vivia Yazhini Sashikumar, Sowmya Ravichandran, Kanishka Padmanaban, Nithya Elango","doi":"10.1007/s12032-025-02637-0","DOIUrl":"https://doi.org/10.1007/s12032-025-02637-0","url":null,"abstract":"<p><p>Over 75% of breast cancers are hormone receptor positive and are associated with better prognosis after treatment, when compared to other types of breast cancer. However, discontinuation of treatment due to side effects is common among one-third of the patients, leading to poor outcomes. On long-term treatment, development of resistance to the current therapeutics is common. CYP17A1, a key enzyme in androgen and estrogen synthesis, is associated in the development and progression of breast cancers. Phytochemicals, which are abundant in three traditional medicinal plants, Fenugreek, Ginger, and Basil, generally used in regulating hormonal disorders were screened for potential inhibition of CYP17A1, by molecular docking (Autodock Vina). The binding affinities were compared with standard CYP17A1 inhibitors Abiraterone and Ketoconazole. Docking analysis revealed that Isovitexin (- 9.5 kcal/mol) and Orientin (- 9.4 kcal/mol) showed comparable binding affinities to Abiraterone and Ketoconazole. Molecular Simulations and MM-GBSA were employed to explore the stability of ligand-protein complexes. Isovitexin had stable interactions with the CYP17A1 than Orientin evident from the RMSD, RMSF, Protein-Ligand contacts and MM-GBSA values. In silico ADMET profiles of the phytochemicals and standard breast cancer drugs (Letrozole, Tamoxifen, Paclitaxel, and Docetaxel) were evaluated using Swiss ADME and pkCSM and found to be similar. In in vitro assays, Isovitexin was found to be cytotoxic to MCF-7 cells, causing 46% apoptosis at < 10 nM levels. The study reveals that Isovitexin, with high cytotoxicity, may be effective in the treatment of both ER- and PR-positive (MCF-7) cancers. Overall, the findings have implications for the therapeutic development of hormone receptor-positive breast cancers.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"137"},"PeriodicalIF":2.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730737","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":"Effect of PRKD3 on cell cycle in gastric cancer progression and downstream regulatory networks.","authors":"Shuaiyang Wang, Bei Xie, Haohua Deng, Xingyuan Ma, Baoyuan Tang, Lei Ma, Jinmei Zhu, Jing Li, Linjing Li","doi":"10.1007/s12032-025-02663-y","DOIUrl":"https://doi.org/10.1007/s12032-025-02663-y","url":null,"abstract":"<p><p>Protein kinase D3 (PRKD3), belonging to the protein kinase D family, significantly influences tumor development and progression. The role of PRKD3 in advancing gastric cancer (GC) and its effects on the cell cycle are not well understood, necessitating detailed investigation. Assessment of PRKD3 expression in both malignant and normal gastric tissues was performed using bioinformatics databases. The influence of PRKD3 on GC's malignant characteristics was evaluated through in vitro experiments utilizing cell line models of GC. Additionally, proteomic analyses were conducted to investigate the potential mechanisms of PRKD3 in GC progression. PRKD3 was notably overexpressed in GC tissues, correlating with adverse outcomes for patients. PRKD3 knockdown impaired GC cell malignancy, manifesting as a 2.12-fold decline in proliferation(p < 0.01), 2.64-fold suppression of migration(p < 0.01), 2.16-fold inhibition of invasion(p < 0.01), and G2/M phase arrest. Proteomic and Western blot analyses had revealed a substantial enrichment in differentially expressed proteins (DEPs) associated with tumor-related signaling pathways, including FoxO and p53, which was paralleled by significant alterations in the levels of key cell cycle proteins such as CDK1, CyclinB1, CHK1 and PLK1, with a 6.8-fold elevation in CHK1 levels(p < 0.05). The overexpression of PRKD3 was intricately linked with the aggressive behaviors of GC. Targeting PRKD3 activity offers potential for effective treatments of GC.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"135"},"PeriodicalIF":2.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710548","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":"Gastrointestinal perforation in general oncology, metastatic colorectal cancer, and metastatic melanoma population.","authors":"Arun Parashar, Vineet Mehta, Varsha Sharma, Muskan Thakur","doi":"10.1007/s12032-025-02691-8","DOIUrl":"https://doi.org/10.1007/s12032-025-02691-8","url":null,"abstract":"<p><p>Gastrointestinal perforation (GIP) is a rare and potentially fatal adverse event of antineoplastic therapy. GIP is a rare but serious complication in oncology patients, often leading to significant morbidity and mortality. In general oncology patients, the incidence of GIP ranged from 0.5 to 1.9%. A meta-analysis of six clinical trials with 4579 patients reported an incidence of 1.0%. Among mCRC patients, the incidence varied between 0.5 and 2.4%, with geographic differences-1.5% in the USA and 2.4% in Australia. For metastatic melanoma patients, the incidence of GIP ranged from 0.4 to 0.67%, with U.S. rates of 0.57% and 0.67% and a lower rate of 0.40% reported in Germany. The findings suggest that the risk of GIP varies significantly across oncology populations and treatment regimens, with higher risks noted in metastatic cancer patients undergoing therapies such as VEGF inhibitors or immune checkpoint inhibitors. These data highlight the need for careful monitoring and early intervention in high-risk populations to reduce the impact of GIP on patient outcomes. This systematic review aims to summarize the incidence of GIP in general oncology, metastatic colorectal cancer (mCRC), and metastatic melanoma (MM) populations. A literature search was conducted in Embase and Medline databases from January 1, 2011 to August 30, 2017, identifying relevant studies on GIP incidence.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 5","pages":"133"},"PeriodicalIF":2.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710553","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}