Nasopharyngeal Carcinoma

P1, N=18, Not yet recruiting, Zhejiang University

Our results revealed the antitumor effect of arenobufagin in vitro and in vivo. Arenobufagin may provide clinical utility on NPC due to the suppression of claspin and the JNK pathway.

These findings establish a novel role of the circCDYL2/EIF3D/RAD51 axis in nasopharyngeal carcinoma radiotherapy resistance. Our work not only sheds light on the underlying molecular mechanism but also highlights the potential of circCDYL2 as a therapeutic sensitization target and a promising prognostic molecular marker for nasopharyngeal carcinoma.

Nasopharyngeal cancer immunotherapy research has mainly focused on immune checkpoint inhibitors and the tumor microenvironment. Notably, China has made significant contributions to this field.

Given its multifaceted mechanisms and preclinical efficacy, Arnicolide D warrants further investigation in clinical settings to validate its therapeutic utility against cancer. The evidence presented underscores the need for rigorous pharmacokinetic and toxicological studies to establish safe dosing parameters for future clinical trials.

Astaxanthin significantly suppresses NPC cell proliferation, cell cycle arrest, migration, invasion while promoting cell apoptosis by inactivating PI3K/AKT and NF-κB pathways. The study first reveals the anticancer role of astaxanthin in NPC, providing a potential candidate for NPC treatment.

In conclusion, CAFs inhibited ferroptosis to decrease DDP sensitivity in NPC through secreting FGF5 and activating downstream FGFR2/Nrf2 signaling. The therapeutic strategy targeting FGF5/FGFR2 axis from CAFs might augment DDP sensitivity, thus decreasing the side effects of DDP in NPC treatment.

Benchmark results showed TMBstable's superior stability with the lowest variance and coefficient of variation across performance metrics, highlighting its effectiveness in analyzing the counting-based biomarker. The TMBstable algorithm can be accessed at https://github.com/hello-json/TMBstable for academic usage only.

Immunohistochemistry and immunofluorescence staining confirmed positive expression of CD71 and the uptake of HFn in C666-1 tumor tissues. In conclusion, our experiments demonstrated that [64Cu]Cu-NOTA-HFn possesses a very high target engagement for CD71-positive NPC tumors and provided a fundamental basis for further clinical translation.

This study highlights the prognostic significance of TNF-α and NLR in NPC patients, especially in those with liver metastasis. These inflammatory markers could serve as valuable indicators for assessing the prognosis of NPC patients. Further research is warranted to validate their clinical utility and explore potential therapeutic implications.

Our findings showed that HOXB2 acts as a tumor promoter in NPC, activating malignant behaviors and radioresistance of tumors via FOXO1 regulation. Moreover, the inactivation of HOXB2 or activation of FOXO1 are potential strategies to inhibit tumor progression and overcome radioresistance in NPC.

Salivary CASTLE is a rare tumor, it should be distinguished from lymphoepithelial carcinoma and squamous cell carcinoma. The patients often have better prognosis and CD5 protein expression has a valuable role in the differential diagnosis.

P3, N=450, Active, not recruiting, Sun Yat-sen University | Not yet recruiting --> Active, not recruiting | Trial completion date: Mar 2027 --> May 2028 | Trial primary completion date: Mar 2024 --> May 2026

P3, N=424, Recruiting, Sun Yat-sen University | Not yet recruiting --> Recruiting

P1, N=12, Not yet recruiting, Sun Yat-sen University

[68 Ga]pentixafor is a promising imaging tracer for detecting primary and metastatic NPC. [68 Ga]pentixafor PET/CT is comparable to [18F]FDG PET/CT in the detection rate of primary tumors and metastatic cervical lymph nodes in nasopharyngeal carcinoma, but [68 Ga]pentixafor uptake was heterogeneous. [68 Ga]pentixafor PET/CT may help select patients most likely to benefit from CXCR4-directed endoradiotherapy.

In this large studied North African population, our findings suggest that the functional CYP2E1, CYP2A6, GSTM1 and GSTT1 variations did not influence NPC susceptibility.

P=N/A, N=470, Completed, Sun Yat-sen University

To conclude, our findings delineate that circCOL1A1 exerts its oncogenic influence in NPC through the modulation of the miR-370-5p/PTMA signaling axis.

P1, N=98, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: May 2025 --> Sep 2024 | Trial primary completion date: May 2025 --> Sep 2024

P2, N=60, Not yet recruiting, Zhejiang Cancer Hospital

EMT activation was present in the radiation-resistant cell line 5-8FR, and was accompanied by the significant enhancement of proliferation, migration and invasion. The BMAL1 gene significantly increased the radiosensitivity of the radiation-resistant cell line 5-8FR and reversed the acquired radio-resistance of NPCs, which was accomplished by inhibiting the TGF-β1/Smads/Snail1 axis-mediated EMT.

The T cells were CD4- and CD8-positive, predominantly intratumoral, and the CD4:CD8 ratio was 1:1 for 75% of the undifferentiated subtype and 89% for differentiated non-keratinized squamous cell carcinoma. All subtypes of nasopharyngeal carcinoma presented with an inflammatory infiltrate with numerous plasma cells, eosinophils, and dendritic cells, presenting as antigen CD1a- and CD68-positive, as well as in CD117-positive mast cells.

The combination of HDW and AP targets 16 key genes to impede the development of NPC, primarily by modulating AKT1 and VEGFA pathways.

This study presents a prognostic model utilizing IMRGs in NPC, which could assist in assessing patient prognosis and provide insights into new therapeutic targets for NPC.

P=N/A, N=10400, Not yet recruiting, Sun Yat-sen University

P3, N=450, Active, not recruiting, Sun Yat-sen University | Recruiting --> Active, not recruiting

Therefore, BRCC3 helped the overexpressed PPP1CC to maintain its high protein level, thereby sustaining the elevation of DNA repair capacity and radioresistance. Our study identified the molecular mechanism by which PPP1CC promotes NHEJ-mediated DNA repair and radioresistance, suggesting that the BRCC3-PPP1CC-Ku70 axis is a potential therapeutic target to improve the efficacy of radiotherapy.

P2, N=162, Recruiting, Sun Yat-sen University | Not yet recruiting --> Recruiting

Our study demonstrated that impaired production of TLR4 seems to be a risk factor of NPC development but functional studies are needed to confirm these findings. As to rs1927914 AA appears to be a good biomarker for better survival in a patient with NPC.

P2, N=50, Not yet recruiting, Sun Yat-sen University

P3, N=298, Recruiting, Akeso | Trial primary completion date: Dec 2023 --> Feb 2025

P=N/A, N=1327, Completed, Taichung Veterans General Hospital

Mechanistically, PQR309 sensitized NPC to gemcitabine by increasing caspase pathway-dependent apoptosis, blocking GSK-3β and STAT3/HSP60 signaling, and ablating epithelial-mesenchyme transition. Thus, targeting PI3K/mTOR using PQR309 might represent a treatment option to promote the response to gemcitabine in NPC, and provides a theoretical foundation for the study of targeted drugs combined with chemotherapy for NPC.

He underwent total laryngectomy with partial pharyngectomy after clinico-radiological evaluation and biopsy. His final diagnosis was lymphoepithelial carcinoma and IHC was positive for pancytokeratin and p63.

P2, N=28, Completed, Akeso | Recruiting --> Completed | N=90 --> 28 | Trial completion date: Jun 2023 --> Dec 2023

Here, we describe the generation of a novel type of DC, CD137L-DC, which are generated from monocytes by stimulation with a CD137 ligand agonist, and that proved to be more potent than classical mo-DC in inducing cytotoxic responses against tumor associated viruses, such as EBV and HBV in vitro. In a phase I clinical trial on patients with locally recurrent or metastatic NPC, a CD137L-DC-EBV vaccine showed good tolerability and prolonged patient survival, providing a basis for further development of CD137L-DC vaccines for immunotherapy.

In NPC cells, PRDX1 and beta-catenin were regulated through LMP2A expression, which reduced cell growth through cell cycle-related gene expression. This study suggests that LMP2A could be a target molecule for inhibiting cancer progression in NPC cells infected with EBV.

In clinical lymphoma samples, the expression of METTL3, YTHDF1 and TLR9 was highly correlated with immune cells infiltration. This study reveals a novel mechanism that EBV represses the important innate immunity molecule TLR9 through modulating the host m6A modification system.

P=N/A, N=214, Recruiting, Jinsheng Hong | Trial completion date: Jul 2023 --> Sep 2025 | Trial primary completion date: Apr 2023 --> Jul 2025

In vivo studies further confirmed that miR-296-5p promotes the sensitivity of NPC cells to DDP treatment. miRNA-296-5p enhances the drug sensitivity of nasopharyngeal carcinoma cells to cisplatin via STAT3/KLF4 signaling pathway.

Furthermore, the study identified the loss of other genes related to cancer and immune pathways, emphasizing the complexity of NPC genomics. In conclusion, this study underscores the significance of MHC class I gene loss and its probable correlation with the cold tumour phenotype observed in NPC.