81. Mature tertiary lymphoid structures linked to HPV status and anti-PD-1 based chemoimmunotherapy response in head and neck squamous cell carcinoma.
作者: Lizao Zhang.;Siqi Ren.;Tianjun Lan.;Ventin Marco.;Niu Liu.;Bin Wei.;Yunsheng Chen.;Jiaying Wu.;Qunxing Li.;Fan Wu.;Peichia Lu.;Jiahao Miao.;Hsinyu Lin.;Xinhui Wang.;Jianglong Zhong.;Jinsong Li.;Song Fan.
来源: Oncoimmunology. 2025年14卷1期2528109页
Mature tertiary lymphoid structures (TLSs) are immune aggregates associated with immune checkpoint blockade (ICB) responses in various cancers, yet their role in chemoimmunotherapy response in head and neck squamous cell carcinoma (HNSCC) remains unclear. By analyzing TCGA-HNSC transcriptomic data and pathology slides, we identified an immune subtype enriched in TLSs, predominantly in HPV-positive tumors, which correlated with favorable immunotherapy response. Single-cell and spatial transcriptomics further revealed distinct TLS compositions, with mature TLSs enriched in germinal center B cells, follicular helper T cells, and resident memory CD8 T cells, while immature TLSs contained FCRL4+ B cells and peripheral helper T cells. Multispectral immunohistochemistry, flow cytometry, and ELISA validated these findings. Notably, neoadjuvant chemoimmunotherapy promoted mature TLS formation. These results suggest that TLS maturity correlates with HPV status and response to anti-PD-1-based chemoimmunotherapy, providing insights for potential therapeutic strategies in HNSCC.
82. Case Report: Guselkumab treatment for sintilimab-exacerbated psoriasis in a cancer patient.
作者: Jianhao Ke.;Meiliang Guo.;Xuan Zhao.;Na Liu.;Qinqin Meng.;Hui Deng.
来源: Front Immunol. 2025年16卷1573495页
Psoriasis is a chronic inflammatory skin disease associated with multisystem comorbidities and impaired mental health. The lesions are typically characterized by sharply demarcated, erythematous plaques covered with silvery scales. Treatment options include topical agents, phototherapy, systemic therapies, and biologic agents. Traditional systemic treatments are generally contraindicated in patients with cancer due to their immunosuppressive effects. Although biologics are widely used in the management of psoriasis, their safety in patients with malignancy remains insufficiently evaluated, as individuals with cancer are typically excluded from clinical trials due to concerns about cancer progression. We report the case of a 61-year-old man whose psoriasis markedly worsened following treatment with sintilimab for pulmonary metastases secondary to colon cancer. The patient was successfully treated with guselkumab, an interleukin (IL)-23 inhibitor, resulting in significant improvement in psoriasis symptoms, while the pulmonary condition remained stable during follow-up after completion of standard cancer therapy. This case highlights the potential utility of IL-23 inhibitors as safe and effective treatment options for patients with concomitant psoriasis and malignancy.
83. Total neoadjuvant immunochemotherapy for proficient mismatch repair or microsatellite stable locally advanced rectal cancer.
Our goal was to assess the efficacy of integrating PD-1 inhibitors with total neoadjuvant treatment (iTNT) in enhancing complete response (CR) rates and the propensity for watch-and-wait (WW) strategies in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC).
84. Thyroid disorders as predictors of cemiplimab efficacy in recurrent/metastatic cervical cancer: real-world evidence from Poland.
作者: Renata Pacholczak-Madej.;Maja Lisik-Habib.;Radosław Mądry.;Monika Szarszewska.;Zuzanna Borysiewicz.;Katarzyna Gabalewicz.;Ewa Iwańska.;Wiktor Szatkowski.;Mirosława Puskulluoglu.;Jerzy Jakubowicz.;Paweł Blecharz.
来源: Front Immunol. 2025年16卷1604826页
Immune checkpoint inhibitors have improved survival in patients with recurrent or metastatic cervical cancer (r/mCC), yet reliable predictors of treatment efficacy remain undefined. Immune-related adverse events (irAEs) have been suggested as potential predictors of response, but evidence in cervical cancer is limited.
85. Structural insights and biomedical potential of biosynthesized silver nanoparticles: antibacterial activity, anti-biofilm and cancer cell inhibition.
作者: Ikram Jemel.;Najeh Krayem.;Hajer Jlidi.;Abir Ben Bacha.;Mona Alonazi.;Raihane Charguia.;Areej Ali Alzahrani.;Sami Aifa.;Sami Mnif.
来源: PeerJ. 2025年13卷e19608页
The increasing threat of antimicrobial resistance and cancer has driven the search for new therapeutic agents, with plant-based biosynthesis of nanoparticles emerging as a promising approach. Silver nanoparticles (AgNPs) synthesized from plant extracts have gained attention for their potential biomedical applications.
86. ROS-Responsive Nanosystem Targeted Co-Delivery YC-1 and Regorafenib to Alleviate Hypoxia Enhancing Hepatocellular Carcinoma Therapy.
作者: Liming Song.;Yahui Wu.;Senfeng Zhao.;Yin Liu.;Zhipu Liu.;Yunpeng Zhai.;Jiahui Cao.;Yaning Xia.;Ruopeng Liang.;Weijie Wang.;Rongtao Zhu.;Binghua Sun.;Yupeng Shi.;Yuling Sun.
来源: Int J Nanomedicine. 2025年20卷8481-8496页
The current treatment of hepatocellular carcinoma (HCC) is confronted with anoxic drug resistance and significant side effects. To address these issues, a Reactive Oxygen Species (ROS)-responsive and targeted nano drug delivery system named REG/YC-1@PTP-RGD NPs (RYP-RGD NPs) was designed for the co-delivery of Regorafenib (REG) and the hypoxia inhibitor 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1).
87. Emerging Trends in the Application of Nanosuspension-Based Biomaterials for Anticancer Drug Delivery.
作者: Mohamed Mahmud E Aldeeb.;Gofarana Wilar.;Cecep Suhandi.;Ahmed Fouad Abdelwahab Mohammed.;Safwat A Mahmoud.;Khaled M Elamin.;Nasrul Wathoni.
来源: Int J Nanomedicine. 2025年20卷8587-8607页
The treatment of cancer remains a formidable challenge, largely due to the difficulty in achieving efficient co-delivery of chemotherapeutic and immunotherapeutic agents to specific tumor sites. Nanosuspension-based biomaterial drug delivery systems for anti-cancer (NBDDSC) have emerged as promising platforms for enhancing drug solubility, stability, and targeted delivery. These systems can be categorized into natural polymer-based, synthetic polymer-based, and hybrid nanosuspensions, each offering distinct advantages in biocompatibility, drug loading, and controlled release. However, the majority of existing NBDDSC rely on synthetic materials that function primarily as excipients, offering no intrinsic therapeutic value. These materials often require intricate manufacturing processes, which can result in issues with batch consistency, reduced stability, and diminished therapeutic efficacy. Additionally, the potential side effects associated with synthetic components further underscore the limitations of these systems. This review explores various preparation methods for nanosuspensions, including antisolvent precipitation, high pressure homogenization, and ultrasonication, highlighting their impact on particle size, drug encapsulation, and stability. Furthermore, the targeted applications of these nanosuspensions in treating of cancers such as glioma is discussed to emphasize their potential clinical relevance. By addressing current limitations, this review underscores the critical importance of simpler, safer, and clinically translatable NBDDSC in advancing cancer therapy.
88. Mechanistic Insights into Flavonoid Subclasses as Cardioprotective Agents Against Doxorubicin-Induced Cardiotoxicity: A Comprehensive Review.
作者: Wei Shang.;Xin-Hui Li.;Lang-Hong Zeng.;Zhi Li.;Yu Hu.;Hui-Min Wen.;Feng-Jun Cao.;Guo-Xing Wan.
来源: Drug Des Devel Ther. 2025年19卷5553-5596页
Doxorubicin (DOX) is an anthracycline chemotherapeutic agent widely used for treating various malignancies due to its remarkable efficacy. However, the dose-limiting cardiotoxicity induced by DOX remains a critical clinical concern with limited therapeutic strategy. Several molecular mechanisms underlying the pathogenesis of doxorubicin-induced cardiotoxicity (DIC) have been proposed, including oxidative stress, dysregulation of Top2β, mitochondrial damage, imbalance of calcium homeostasis, ferroptosis, and inflammatory responses. Increasing studies have posed the promise of the natural products flavonoids against DIC attributed to its advantages in antioxidant activity as well as anti-cancer properties. This paper reviews relevant publications to date and comprehensively summarizes the evidence from preclinical and clinical studies in support of the cardioprotective effect of seven flavonoids subclasses against DIC, including flavones with 18 compounds, flavonols with 11 compounds, isoflavones with 7 compounds, flavanones with 6 compounds, chalcones with 3 compounds, flavanols with 2 compounds and anthocyanins with 2 compounds. Specially, several lines of evidence have also demonstrated the anti-cancer property of flavonoids in addition to the cardioprotective property. This review synthesizes comprehensive mechanistic and translational insights to inform future preclinical and clinical investigations aiming at integrating flavonoid-based interventions into oncotherapeutic regimens. The accumulated evidence underscores flavonoids as promising candidates for DIC as well as adjuvant cancer therapy.
89. Bibliometric and Visualized Analysis of Artemisinin and Its Derivatives in Cancer.
作者: Jiaming Feng.;Yuqing He.;Ting Bai.;Qianhui You.;Huici Zhu.;Chengyao Jia.;Baonian Liu.;Shaoling Li.
来源: Drug Des Devel Ther. 2025年19卷5517-5538页
Artemisinin, found in the traditional Chinese medicine (TCM) Artemisia annua, has demonstrated remarkable efficacy in therapeutics and holds significant potential as a pharmaceutical drug in cancer. Until now, there have been no systematic scientometrics studies to analyze the research trend of artemisinin and its derivatives in cancer.
90. Midkine Promotes Tumor Growth and Attenuates the Effect of Cisplatin in Small Cell Lung Cancer.
作者: Shotaro Ito.;Jun Sakakibara-Konishi.;Mineyoshi Sato.;Tetsuaki Shoji.;Megumi Furuta.;Hirofumi Takahashi.;Kosuke Tsuji.;Daisuke Morinaga.;Masahiro Kashima.;Hidenori Kitai.;Junko Kikuchi.;Eiki Kikuchi.;Kanako C Hatanaka.;Yutaka Hatanaka.;Kyoko Hida.;Takuro Noguchi.;Satoshi Konno.
来源: Cancer Med. 2025年14卷13期e71034页
Small cell lung cancer (SCLC) is a highly aggressive disease associated with poor patient survival rates. The addition of an anti-programmed death ligand 1 antibody to platinum combination chemotherapy can improve its prognosis. However, only a few patients achieve a long-term response; thus, establishing new therapies for SCLC is crucial. Midkine (MDK) is a heparin-binding growth factor involved in various biological processes, including cell proliferation and chemotherapeutic resistance, in diverse cancers. MDK has garnered attention as a therapeutic and diagnostic target for several cancers; however, only a few studies have evaluated its expression and function in SCLC. This study aimed to evaluate the MDK expression in human SCLC tissue and human SCLC cell lines, and to clarify its function in tumorigenesis.
91. Immune Checkpoint Inhibitor-Related Dysautonomia in Merkel Cell Carcinoma: A Case Report.
作者: Nidhi Kuchimanchi.;Sai Gajula.;Elizabeth M Gaughan.;Russell G Witt.
来源: Cancer Rep (Hoboken). 2025年8卷7期e70274页
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block inhibitory pathways that cancer cells exploit to suppress T-cell activation. Although immune-related adverse events (irAEs) linked to ICI therapy are well documented and encompass dermatologic, endocrine, gastrointestinal, hepatic, and neurologic systems, ICI-related dysautonomia remains a rare phenomenon. Management of ICI-related dysautonomia is undefined.
92. Synthesis and Biological Activity of Benzoselenazole and Benzo[b]Selenophene Analogues: A Review.
作者: Jia Li.;Jingmin Chen.;Jiayao Liu.;Xudong Zhou.;Yangyang Li.;Wei Wang.;Wenbing Sheng.
来源: Drug Dev Res. 2025年86卷5期e70127页
Selenium, an essential micronutrient in the human body, not only exhibits potent antioxidant properties but also plays a critical role in regulating thyroid hormone metabolism, maintaining normal immune function, and inhibiting tumour progression. Among selenium-containing compounds, ebselen is the most extensively studied drug candidate. Research has shown that various derivatives obtained through structural modifications of Ebselen exhibits significant biological activities; however, these compounds have yet to progress to clinical trials. Consequently, selenium-containing heterocyclic compounds represent a promising avenue for drug discovery and development. This review summarizes three synthetic approaches for constructing selenium-containing heterocyclic compounds and emphasizes their notable biological activities and potential applications in pharmaceuticals.
93. Rosmarinic acid potentiates gefitinib in lung adenocarcinoma by modulating interactions between cancer cells and cancer-associated fibroblasts.
While cancer-associated fibroblasts (CAFs) significantly influence tumor progression, their temporal dynamics remain poorly understood. We investigated time-dependent interactions between non-small cell lung cancer (NSCLC) cells and CAFs, and evaluated rosmarinic acid (RA)'s potential to modulate these interactions. HCC827 lung adenocarcinoma cells and MRC-5 fibroblasts were co-cultured in vitro. CAF activation markers (α-SMA, FAP) and epithelial-mesenchymal transition (EMT) were assessed through morphological and molecular analyses. Xenograft models with different tumor-to-fibroblast ratios (1:1, 1:2) evaluated tumor growth dynamics and RA's therapeutic effects combined with gefitinib. Time-course analysis revealed a biphasic pattern in tumor-CAF interactions. CAF activation markers reached peak levels by day 6, followed by maximal EMT marker expression in NSCLC cells at day 8. In xenograft models, higher CAF proportions initially inhibited tumor growth but accelerated tumor progression. RA treatment significantly attenuated CAF activation markers and reversed EMT-related changes in cancer cells, leading to reduced tumor growth in CAF-enriched xenografts. The combination of RA with gefitinib demonstrated enhanced anti-tumor effects compared to gefitinib alone. CAFs exhibit temporally biphasic roles in NSCLC progression characterized by initial suppression followed by promotion of tumor microenvironment deterioration. RA effectively modulates these tumor-stromal interactions, enhances gefitinib efficacy, and delays the development of drug resistance.
94. THEM6 modulates carboplatin sensitivity by regulating ferroptosis through FDFT1 in triple-negative breast cancer.
作者: Yuexiang Zeng.;Zhijie Xu.;Juan Huang.;Qiaoli Yi.;Xi Chen.;Jiayu Wang.;Zhihao Du.;Jian Tian.;Yuanliang Yan.
来源: Breast Cancer Res. 2025年27卷1期124页
Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis, as chemotherapy resistance leads to relapse in many patients. Carboplatin addition improves treatment response, but challenges persist.
95. Recognition of cancer chemotherapy adverse effect by patients: a cross-sectional study from Palestine.
作者: Ayah Maqdasawi.;Rawan Ghanayiem.;Marwa Khalaf.;Riad Amer.;Sultan Mosleh.;Ramzi Shawahna.
来源: BMC Cancer. 2025年25卷1期1149页
It has been suggested that patient awareness of chemotherapy-induced side effects is not uniform and may vary according to communication quality between healthcare providers and patients, educational initiatives, and the type of cancer and chemotherapy regimen. This study aimed to assess real-world chemotherapy-induced adverse effects as reported by cancer patients in the West Bank of Palestine and to identify key predictors of these side effects.
96. USP44 promotes chemotherapeutic drug resistance of triple negative breast cancer through EZH2 protein stability.
作者: Pu Wu.;Wanting Xiao.;Junjie Ni.;Yuming Lou.;Chaoyang Xu.
来源: Cancer Biol Ther. 2025年26卷1期2529652页
Triple negative breast cancer (TNBC), a highly invasive breast cancer, is one of the leading causes of cancer-related mortality worldwide. Although chemotherapy remains the standard of care for TNBC, the development of chemotherapy resistance significantly limits its clinical efficacy. In this study, we identified the deubiquitinating enzyme USP44 as a contributor to chemoresistance in TNBC and investigated the potential regulatory feedback mechanisms involved. In this experimental study, we investigated the sensitivity of TNBC cells MDA-MB-231 and BT-549 to chemotherapy drugs after overexpression and knockdown of USP44 using CCK-8 reagent kit and flow cytometry analysis, respectively. Western blot was performed to evaluate the expression levels of relevant proteins. In vivo xenograft models were established to examine the effects of USP44 and its downstream targets on chemosensitivity. Co-immunoprecipitation assay and ubiquitination assay were conducted to identify interacting proteins and elucidate the underlying molecular mechanisms. Knockdown of USP44 increased the sensitivity of MDA-MB-231 and BT-549 cells to chemotherapeutic agents, accompanied by elevated levels of Cleaved PARP. In contrast, USP44 overexpression reduced drug sensitivity. Mechanistically, USP44 was found to interact with EZH2, preventing its ubiquitination and subsequent proteasomal degradation. Notably, treatment with GSK126, a specific EZH2 inhibitor, reversed the chemoresistance induced by USP44 overexpression. USP44/EZH2 signaling pathway is one of the key to causing the drug resistance of TNBC, warranting further clinical investigation.
97. Tanshinone IIA induces ferroptosis in colorectal cancer cells through the suppression of SLC7A11 expression via the PI3K/AKT/mTOR pathway.
作者: Tingrui Ge.;Huazhuan Li.;Ping Xiang.;Dong Yang.;Jingyi Zhou.;Yonggang Zhang.
来源: Eur J Med Res. 2025年30卷1期576页
Colorectal cancer (CRC) is a malignant tumor of the digestive system with high incidence rate and mortality. Tanshinone IIA (Tan IIA) plays an anti-cancer role in a variety of cancer cells. Here, we aimed to elucidate the therapeutic effects and potential mechanism of Tan IIA in CRC.
98. The combination of chemotherapy and immune checkpoint inhibitors in recurrent extensive-stage small cell lung cancer: a case report.
作者: Chunxiu Hu.;Mingtu Zhang.;Min Fang.;Yi Liu.;Zhengqi Yang.
来源: J Cardiothorac Surg. 2025年20卷1期286页
Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases and is characterized by high malignancy, rapid progression, and poor prognosis. Here, we report a case of a 58-year-old female patient who was initially diagnosed with extensive-stage SCLC (ES-SCLC) with liver metastasis. The patient underwent etoposide and cisplatin (EP) chemotherapy combined with local radiotherapy and achieved a complete response. The progression-free survival reached 48 months, and upon relapse, the patient received EP chemotherapy combined with the programmed cell death protein 1 (PD-1) inhibitor, tislelizumab, as immunotherapy. During the treatment period, the patient experienced immune-related pancreatitis, but the symptoms were relieved with timely intervention and treatment. As of January 2, 2024, the patient's overall survival exceeded 95 months. This case highlights the potential efficacy of the combination of chemotherapy and immunotherapy in recurrent ES-SCLC patients and underscores the importance of close monitoring and management of immune-related adverse reactions. The study provides valuable insights into the application of personalized treatment in lung cancer management and offers new possibilities for extending patient survival.
99. Developing a formulation of Tinospora cordifolia, identifying its active components, and assessing its anticancer effects on breast cancer cell lines.
作者: Muhasina K M.;Md Ekhtiar Uddin.;Ravi Naik Mundavath.;Akey Krishna Swaroop.;Shrikant Shivkumar Nilewar.;Esakkimuthukumar Mariappan.;Puja Ghosh.;Deepika N P.;Krishnaveni Nagappan.;Md Shahin Reza.;Mohammed Abdul Kader.;Dhanabal S Palaniswamy.
来源: Med Oncol. 2025年42卷8期312页
Tinospora cordifolia (Willd.) Miers is a medicinal plant recognised for its pharmacological potential. This work presents the development of an innovative nano-liposomal formulation and assesses its anticancer efficacy against breast cancer cell lines. A sustainable green extraction method was employed to isolate bioactive compounds from T. cordifolia, followed by the development of a nano-liposomal formulation. Particle size and morphology were assessed using field emission scanning electron microscopy (FESEM), revealing soft, globular vesicles with an average diameter of ~ 153 nm. GC-MS profiling identified 35 phytoconstituents subjected to molecular docking against topoisomerase IIα to predict anticancer potential. The biological activity of the formulation was validated through MTT assay for cell viability, scratch assay for cell migration, and apoptosis assays in MCF-7 and MDA MB 231 breast cancer cell lines. Immunocytochemistry was used to evaluate the expression of Bcl-2, cytochrome-C, and caspase-3. ROS generation was also quantified to confirm the mechanism of action. In silico analysis identified glucobrassicin as a potent topoisomerase IIα inhibitor (docking score: - 10.2655). The formulation exhibited dose-dependent cytotoxicity, inhibited cell migration, and induced apoptosis in both cell lines. ROS-mediated cell death was associated with increased cytochrome-C and caspase-3 expression and decreased Bcl-2 levels. This study underscores the value of integrating green nanotechnology, computational docking, and functional cell-based assays to identify and characterise the bioactive phytochemicals. The T. cordifolia-based liposomal formulation demonstrated promising anticancer activity and warrants further preclinical evaluation as a candidate for breast cancer therapy.
100. TTK activates ATR through RPA2 phosphorylation to promote olaparib resistance in ovarian cancer.
Resistance to poly(ADP‒ribose) polymerase inhibitors (PARPis) remains a significant challenge in ovarian cancer (OC) treatment. TTK protein kinase (TTK) has been implicated in cisplatin resistance in OC, but its role in PARPi resistance remains unclear. In this research, we found that TTK inhibition overcome olaparib resistance in HR-proficient OC cells, whereas TTK promotes olaparib resistance in HR-deficient OC cells. Mechanistically, TTK directly interacts with RPA2, facilitating phosphorylation of its S33 residue to activate the ATR signaling pathway. Knocking down RPA2 increased olaparib sensitivity in OC cells. Additionally, TTK-mediated resistance to olaparib through the RPA2/ATR signaling pathway was confirmed via both in vitro and in vivo models. In conclusion, TTK inhibition overcomes olaparib resistance in HR-proficient OC cells, in part by suppressing RPA2-S33 phosphorylation and attenuating ATR signaling. TTK inhibitors offer a promising strategy to increase the therapeutic efficacy of PARPis in OC patients.
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