Medical Oncology最新文献

{"title":"Cyclooxygenase-2 as a potential therapeutic target in the treatment of chemoresistant glioblastomas.","authors":"Vladislav S Skossyrskiy, Natalya A Kurdina, Viktoriya S Kuzovkova, Maxim S Boot, Polina I Zelenchenkova, Ekaterina O Popova, Nadezhda V Sevyan, Alexey A Mitrofanov, Evgeniy V Prozorenko, Marina I Sekacheva, Ekaterina V Orlova","doi":"10.1007/s12032-025-03000-z","DOIUrl":"https://doi.org/10.1007/s12032-025-03000-z","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) remains one of the most lethal malignancies due to its marked resistance to standard therapies and a profoundly immunosuppressive tumor microenvironment. Cyclooxygenase-2 (COX-2), via its enzymatic product prostaglandin E2 (PGE2), has emerged as a central driver of multiple oncogenic processes in GBM, including immune evasion, therapy resistance, glioma stemness, and vascular mimicry. This review consolidates recent molecular findings on the COX-2/PGE2 axis, with particular focus on EP2/EP4-mediated signaling pathways such as PI3K/AKT, MAPK, β-catenin/TCF4, and JAK/STAT3, which collectively contribute to tumor proliferation, radioresistance, and PD-L1 expression. Notably, COX-2 promotes extracellular matrix degradation and glioma invasiveness by upregulating matrix metalloproteinase-9 (MMP-9) through TGF-β1 derived from tumor-associated macrophages (TAMs). In parallel, COX-2 facilitates TAM polarization toward an M2-like phenotype and supports the self-renewal of glioblastoma stem cells (GSCs), reinforcing both immune suppression and therapeutic escape. Furthermore, recent data reveal that COX-2 inhibition by celecoxib contributes to mitochondrial dysfunction by downregulating respiratory complexes and mitochondrial biogenesis regulators such as TFAM and NRF2, ultimately leading to bioenergetic collapse and sensitization to chemotherapy-induced apoptosis. By integrating diverse yet interconnected mechanisms under the umbrella of COX-2 signaling, this review outlines potential therapeutic opportunities aimed at disrupting its multifaceted role in GBM pathogenesis and treatment resistance.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 12","pages":"530"},"PeriodicalIF":3.5,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145368058","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":"Silencing SOX2OT reduces viability and migration in lung cancer cells via lncRNA and protein regulation.","authors":"Mohadeseh Zarei, Ali Dinari, Babak Jahangiri, Elahe Asadollahi, Jamshid Raheb","doi":"10.1007/s12032-025-03085-6","DOIUrl":"https://doi.org/10.1007/s12032-025-03085-6","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) play crucial role in tumor development and are being explored as potential therapeutic targets in lung cancer. Both SOX2OT and SOX2 are consistently overexpressed in lung cancer, suggesting that SOX2OT may play a significant role in its development. This study examines how knocking down SOX2OT affects the expression of specific lncRNAs (LINC00982, LINC00668, SNHG7), the gene P16, and key cell cycle-regulating proteins (HSP90AA1, EP300, YES1) in lung cancer cells. Silencing of SOX2OT in A549 and Calu-3 cells led to a marked reduction in its expression. This downregulation was accompanied by decreased levels of SNHG7 and LINC00668, while LINC00982 and P16 transcripts were strongly induced. At the protein level, EP300, HSP90AA1, and YES1 were substantially reduced, whereas P16 was notably elevated. Functionally, suppression of SOX2OT impaired cell viability and significantly limited migratory capacity. In parallel, apoptosis assays demonstrated a pronounced increase in apoptotic cell populations following SOX2OT knockdown. SOX2OT regulates specific lncRNAs and proteins involved in lung cancer survival and migration. Silencing SOX2OT significantly reduces viability, migration, and survival of lung cancer cells, suggesting its potential as a therapeutic target. Further in vivo validation and rescue experiments are needed to confirm these mechanisms.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 12","pages":"528"},"PeriodicalIF":3.5,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355277","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 role of transforming growth factor-β in glioblastoma: a focus on phytochemicals.","authors":"Ali Nakhaei, Mehdi Abedi, Sadaf Afshari, Alireza Mohtashami, Mohammad Jalili-Nik, Mahsa Jalali, Amir R Afshari","doi":"10.1007/s12032-025-03090-9","DOIUrl":"https://doi.org/10.1007/s12032-025-03090-9","url":null,"abstract":"<p><p>Glioblastoma (GBM), the most aggressive type of primary brain tumor in adults, is characterized by a poor prognosis and considerable resistance to current therapies. Traditional treatment approaches-surgery, radiation, and chemotherapy-offer few clinical benefits and are often linked to increased recurrence rates and significant adverse effects. This underscores the urgent need for novel therapeutic strategies. Targeting the transforming growth factor-beta (TGF-β) signaling pathway is a viable strategy. TGF-β acts as a tumor suppressor during the first stages of cancer but promotes tumor progression, angiogenesis, immune evasion, and the creation of an immunosuppressive tumor microenvironment in GBM. The deregulation of TGF-β signaling has been shown to interact with essential carcinogenic pathways, including the Wnt/β-catenin, PI3K/AKT, and Notch pathways, therefore aggravating GBM pathogenesis. TGF-β plays a pivotal role in controlling glioma stem cells and influencing the permeability of the blood-brain barrier, making it an attractive target for therapeutic intervention. Novel treatment approaches, including small-molecule inhibitors and monoclonal antibodies, as well as the use of phytochemicals such as flavonoids, quercetin, and other phytochemicals targeting specific elements of the TGF-β signaling pathway, have shown encouraging results in preclinical investigations and early-stage clinical trials. These novel strategies may enhance clinical outcomes and mitigate treatment limitations in GBM therapy by leveraging this system's combined tumor-suppressive and immune-regulatory properties.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 12","pages":"529"},"PeriodicalIF":3.5,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355250","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":"Optimization of upfront therapy for adult acute lymphoblastic leukemia: a paradigm shift toward immunotherapy.","authors":"Amr Hanbali, Mostafa Saleh, Mohamed Kharfan-Dabaja, Ahmed Abdrabou, Riad El Fakih, Mansour Alfayez, Anjali Advani, Mahmoud Aljurf","doi":"10.1007/s12032-025-03093-6","DOIUrl":"https://doi.org/10.1007/s12032-025-03093-6","url":null,"abstract":"<p><p>Adult acute lymphoblastic leukemia (ALL) treatment protocols are evolving with frontline therapy now incorporates targeted immunotherapeutic agents. Targeted immune therapies like blinatumomab, inotuzumab ozogamicin (InO), rituximab, and nelarabine are being combined with traditional chemotherapy protocols to enhance remission rates and minimal residual disease (MRD) negativity while decreasing toxicities. The incorporation of blinatumomab into initial treatment protocols for both Philadelphia chromosome-negative (Ph -) and positive (Ph +) ALL patients results in notable early MRD elimination. The medical use of InO as an initial treatment has increased specifically for older or medically unfit patients. The addition of rituximab to chemotherapy treatment in CD20-positive B-ALL patients produces superior long-term results. Adding nelarabine to pediatric-inspired T-cell ALL treatment protocols in young adult and adolescent (AYA) patients resulted in decrease their risk of central nervous system (CNS) relapse. High-risk ALL subtypes including Ph + and Ph-like ALL now receive immunotherapeutic and molecularly targeted treatments. Ph + ALL patients receive standard treatment with multi-agent chemotherapy and TKIs dasatinib or ponatinib and blinatumomab as part of their frontline therapy to enhance molecular responses and minimize the requirement for allogeneic hematopoietic stem cell transplantation (allo-HCT). The combination of JAK inhibitors with ABL-class TKIs, chemotherapy, and immunotherapy represents current early-phase trial approaches for Ph-like ALL patients with kinase-activating alterations. The practice of testing MRD and genomic profiling at diagnosis revolutionized treatment approaches by allowing personalized curative strategies for all patients. Research on clinical trials aims to establish the best sequence of targeted therapies and CAR T-cell therapy for high-risk and MRD-positive patients to achieve longer survival rates with reduced toxicity and less dependence on allo-HCT in first remission.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"526"},"PeriodicalIF":3.5,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345886","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 trio of Candida albicans, immune cells, and cancer progression: a complex interplay driving tumorigenesis.","authors":"Rashi Verma, Pallavi Saxena, Luqman Ahmad Khan","doi":"10.1007/s12032-025-03089-2","DOIUrl":"https://doi.org/10.1007/s12032-025-03089-2","url":null,"abstract":"<p><p>Candida albicans (C. albicans) has been identified as an opportunistic pathogen that resides as commensal in healthy population but transform into pathogen in immunocompromised individuals. Beyond secondary infection, current studies are evident it's complicated and concerning association in cancer progression. However, the interplay behind this association is still unknown. Here, we explored the trio association between the host's immune response, C. albicans and cancer progression. We acknowledged the gaps in existing knowledge, particularly the understudied mechanisms through which C. albicans promote oncogenesis and tumor progression. Key areas included chronic inflammation, influence on tumor microenvironment, immune modulation, and biofilm formation. Additionally, the review uncovered novel insights that could highlight the necessary future directions, specifically in development of therapeutics targeting this triad for better cancer management.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"527"},"PeriodicalIF":3.5,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345913","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":"Box-Behnken-designed nanostructured lipid carriers of xanthohumol for enhanced cellular uptake in human lung cancer cell line A549: formulation, optimization, characterization, and cytotoxicity assessment.","authors":"Shubham Singh, Himani Sharma, Madan Kumar Arumugam, Gaurav Gupta, Nisha Panth, Mangesh Pradeep Kulkarni, Gabriele De Rubis, Brain G Oliver, Keshav Raj Paudel, Narendra Kumar Pandey, Md Sadique Hussain, Popat S Kumbhar, John Disouza, Kamal Dua, Sachin Kumar Singh","doi":"10.1007/s12032-025-03087-4","DOIUrl":"https://doi.org/10.1007/s12032-025-03087-4","url":null,"abstract":"<p><p>The present research aims to develop and optimize nanostructured lipid carriers (NLCs) of Xanthohumol (Xn) for treating lung cancer (LC). Xn packed NLCs were successfully prepared by hot high-pressure homogenization in conjunction with the ultrasonication method and optimized using a pseudo-ternary phase diagram followed by the Box-Behnken design (BBD). The NLCs were solidified using rotary evaporation followed by tray drying/vacuum drying. Mannitol was used for the solidification of L-Xn-NLCs. The BBD was operated using 3 factors and 3 levels for optimization of the formulation. The dependent variables were zeta potential (R1), particle size (R2), and drug entrapment efficiency (R3), while the independent variables were Beeswax (A), Lauroglycol-90 (B), and Tween 80 (C). The optimized liquid NLCs (L-Xn-NLCs) showed particle size (PS) of 101.60 ± 1.47 nm, polydispersity index (PDI) of 0.772 ± 0.029, zeta potential (ZP) of - 25.6 mV, and an entrapment efficiency (% EE) of 97.72 ± 1.05%. As a result, NLCs have a higher drug encapsulation efficiency. After drying, followed by reconstitution, the solid NLCs (S-Xn-NLCs) showed PS of 278 nm, PDI of 0.22, ZP of - 44.3 mV, and EE% of 95.5. The results of SEM and PXRD revealed the complete adsorption of S-Xn-NLCs on the surface of mannitol. The in vitro drug release and in vitro MTT assay were performed on A549 LC cells to evaluate the anticancer efficacy of S-Xn-NLCs. In 24 h, the L-Xn-NLCs, S-Xn-NLCs, and pure drug suspension had a cumulative drug release rate of 80.09 ± 0.8%, 79.8%, and 40 ± 1.1%, respectively. It was found that both pure Xn and S-Xn-NLCs reduced the proliferation of A549 cell lines at 28.21 µM, 56.42 µM, 84.63 µM, 112.84 µM, and 141 µM. However, S-Xn-NLCs exerted higher reduction in proliferation than pure Xn. The pure Xn and the S-Xn-NLCs showed anticancer potential against A549 cell lines and the IC₅₀ was found to be 140.186 µM for the pure Xn and 84.63 µM for the S-Xn-NLCs. The S-Xn-NLCs showed higher cytotoxicity potential to A549 cells as compared to the pure Xn. Thus, it was concluded that the optimized NLCs showed very good efficacy against LC.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"525"},"PeriodicalIF":3.5,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345902","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":"Post-translational modifications in hepatocellular carcinoma: mechanisms and therapeutic potential.","authors":"Jianqi Qin, Weixiong Zhu, Zengxi Yang, Shuze Zhang, Wence Zhou","doi":"10.1007/s12032-025-03079-4","DOIUrl":"https://doi.org/10.1007/s12032-025-03079-4","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC), a prevalent and lethal cancer worldwide, is driven by complex molecular mechanisms. Post-translational modifications (PTMs) crucially influence protein function, stability, and signaling, affecting metabolic reprogramming, cell cycle control, immune evasion, and tumor microenvironment (TME) changes in HCC. Recent studies have increasingly examined various PTMs in HCC, notably phosphorylation, ubiquitination, methylation, glycosylation, acetylation, lactylation, and SUMOylation. These modifications affect key proteins like GPX4, CDK5, PHGDH, GLS1, and HIF-1α, playing roles in cancer development, spread, and treatment resistance. Despite progress, challenges remain in understanding PTMs and applying them clinically. This review aims to summarize recent PTM research in HCC, evaluate their therapeutic potential, and propose strategies for precision therapies in HCC.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"524"},"PeriodicalIF":3.5,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313269","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":"Topical vaginal drug therapy in cervical cancer management: a review of clinical trials and preclinical evidence.","authors":"Chaoqun Li, Yao Zhu, Nan Li, Bing Dai, Jian Wang, Lili Wang, Li-Li Wang, Xiaoling Zheng","doi":"10.1007/s12032-025-02983-z","DOIUrl":"https://doi.org/10.1007/s12032-025-02983-z","url":null,"abstract":"<p><p>Cervical cancer, the fourth most prevalent malignancy among women globally, is predominantly caused by persistent infection with high-risk human papillomavirus (HPV). Traditional methods such as surgery and chemotherapy are often associated with high incidence of adverse effects and may impact future pregnancies and childbirth especially for young female patient. Given that high-risk HPV primarily targets epithelial cells and cervical lesions are mainly localized in the cervix, local administration in the cervicovaginal area emerges as one of the most direct and effective methods for treating cervical cancer and its precursors. Topical vaginal administration not only minimizes systemic drug exposure but also simplifies application, reduces treatment costs, and supports fertility preservation. Nevertheless, there are currently no official recommendations for local therapies targeting HPV eradication or tumor lesion treatment. This review focuses on clinical trials and preclinical studies related to local pharmacotherapy for cervical tumors, with an emphasis on evaluating the efficacy of local treatments aimed at preventing the progression of cervical intraepithelial neoplasia. It encompasses therapeutic agents, clinical efficacy and adverse effects, treatment strategies, and innovations in formulations while also addressing the inherent challenges of vaginal administration and predicting future trends in this therapeutic field. Clinical studies have shown that trichloroacetic acid offers the best patient compliance and therapeutic response, although concerns remain regarding its uncontrolled depth of tissue penetration. In parallel, formulation optimization strategies such as prolonging vaginal residence time and employing nanotechnology to enhance drug loading and targeted delivery have shown promise in improving therapeutic outcomes.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"523"},"PeriodicalIF":3.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313260","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":"Targeted drug delivery in cervical carcinoma: the role of gold nanoparticles in enhancing treatment efficacy.","authors":"Sampada D Dalvi, Mukesh P Ratnaparkhi, Rohan N Badhe, Bhakti S Matkar, Kapil A Kaninde","doi":"10.1007/s12032-025-03088-3","DOIUrl":"https://doi.org/10.1007/s12032-025-03088-3","url":null,"abstract":"<p><p>As the fourth most common cancer affecting women globally, cervical cancer presents a significant health challenge. Nanotechnology offers a promising new frontier for treatment, with gold nanoparticles (AuNPs) emerging as a powerful tool for enhancing therapeutic effectiveness.This review focuses on the synthesis of AuNPs and their strategic application in targeted drug delivery systems to combat cervical cancer. Gold nanoparticles are exceptionally well suited for this role due to a unique combination of properties, including their small size, high surface-area-to-volume ratio, excellent stability, and biocompatibility. These traits make them ideal vehicles for medical use.Beyond targeted drug delivery, AuNPs can also act as radiosensitizers, increasing the susceptibility of cancer cells to radiation. This synergy has the potential to make radiation therapy more precise and effective, highlighting the multifaceted role of gold nanoparticles in developing more advanced and targeted treatments for cervical cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"522"},"PeriodicalIF":3.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313219","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 to: Long noncoding RNA GAS5 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer.","authors":"Dandan Yin, Xuezhi He, Erbao Zhang, Rong Kong, Wei De, Zhihong Zhang","doi":"10.1007/s12032-025-03070-z","DOIUrl":"https://doi.org/10.1007/s12032-025-03070-z","url":null,"abstract":"","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"521"},"PeriodicalIF":3.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308368","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}