Nasopharyngeal Carcinoma

LRRT could prolong PFS in M1-NPC patients. OMD and undetectable EBV DNA2-6 cycles are potential indicators for selecting beneficiaries from LRRT.

Our findings suggest that the AGT-HIF-1α-HILPDA pathway promotes radioresistance in NPC by enhancing lipid droplet accumulation, thereby suppressing ferroptosis. Targeting local Ang II alongside ferroptosis induction offers a promising strategy to improve radiosensitivity in NPC.

Foxa1 disruption in mouse embryos significantly enhances the integration of human cells in human-mouse interspecies chimeras, thereby facilitating the generation of endoderm-derived organs through blastocyst complementation. Overcoming chimeras' embryonic lethality is crucial for successfully generating humanized NE in Foxa1-deficient mouse embryos.

In summary, this study identified TPPP3, MUC4 and CLIC6 as lactate-associated clinical modelling indicators linked to NPC, providing a foundation for advancing diagnostic and therapeutic strategies for this malignancy.

Moreover, Vimentin knockdown significantly mitigates the oncogenic effects induced by overexpression of both KLHDC4-WT and the Glu510Lys variant. Collectively, our findings highlight the critical role of the rare KLHDC4 variant rs141121474 in NPC progression and propose its potential as a diagnostic and therapeutic target for NPC patients.

Notably, FOXP1 overexpression counteracted the suppressive effects induced by transfection with miRNA-22-3p mimic on HK-1 cell viability and migration. Therefore, these data indicate that miRNA-22-3p may be a clinically valuable biomarker for the therapy of NPC.

IFNGR2 is an oncogenic factor in NPC. The circ_001377/miR-498-3p interaction drives IFNGR2 upregulation and PD-L1 overexpression, suggesting that targeting this axis could improve therapeutic outcomes.

Mechanistically, EBV latent membrane protein 1 (LMP1) mediated upregulation of CD55 through the NF-κB signalling pathway. The present study provides a rationale for the development of CD55 inhibitors to improve the clinical efficacy of cetuximab in NPC.

P=N/A, N=167, Completed, Taproot Health | Recruiting --> Completed | N=100000 --> 167 | Trial completion date: Oct 2031 --> Oct 2024 | Trial primary completion date: Oct 2029 --> Oct 2024

HIF-1α could inhibit the proliferation, invasion and metastasis of nasopharyngeal carcinoma by regulating the expression of MMP-2, thus inhibiting tumor growth. Therefore, HIF-1α and MMP-2 might become important therapeutic targets to inhibit the growth, invasion and metastasis of nasopharyngeal carcinoma.

CD47, CD68, and CD163 are significant prognostic markers in NPC, with higher levels being associated with poorer OS and PFS. Elevated MLR and MAR values also predict worse outcomes, underscoring their value as prognostic tools. CD163 and MLR are particularly strong predictors, highlighting the crucial role of TAMs in NPC management and suggesting that CD163 is a potential therapeutic target within the immune checkpoint pathway.

NPC is a rare malignancy with significant geographical variations in incidence rates. Somatostatin receptor 2 (SSTR2) expression in NPC is well documented and can serve as a potential theragnostic marker in advanced NPC where the successful outcome is minimal with currently available treatment modalities.

This study established a novel radiosensitivity-related prognostic model, offering insights into NPC prognosis and radiotherapy resistance mechanisms.

We then detected the epithelial-mesenchymal transition (EMT) markers [i.e., epithelial cadherin (E-cadherin), matrix metallopeptidase 9 (MMP9), vimentin, and snail family transcriptional repressor 1 (SNAIL)], phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK), to identify the potential mechanisms of AKF-PD. AKF-PD not only mitigates CP-induced AKI but also enhances the anti-cancer efficacy of CP. Our findings provide valuable insights into the treatment of NSCLC and may have clinical applications.

68Ga-DOTATATE PET/CT is a promising imaging modality for detecting primary and metastatic EBV-positive nonkeratinizing nasopharyngeal carcinoma and delineating primary tumor boundary.

P2, N=50, Recruiting, National University Hospital, Singapore

This study identifies MYC, FN1, BRCA1, and FGF2 as anoikis-related genes (ARGs) with significant regulatory roles in nasopharyngeal carcinoma (NPC). These ARGs are found to be involved in the development and progression of NPC, suggesting their potential as therapeutic targets for this cancer.

Moreover, high BRD7 expression and low METTL3 expression are positively correlated with radiosensitivity and good prognosis in NPC patients. Taken together, our findings reveal that BRD7 promotes the radiosensitization of NPC cells by negatively regulating USP5/METTL3 axis activity and indicate that targeting the BRD7/METTL3 axis might be a novel therapeutic strategy for NPC radiosensitization.

P2, N=40, Completed, Sun Yat-sen University | Active, not recruiting --> Completed | Trial completion date: Oct 2026 --> Dec 2024

In this study, we developed an LMP2 mRNA vaccine based on a serum-resistant fluorinated polyethyleneimine (TKPF) with self-adjuvant effects to achieve strong anti-tumor immunity in NPC treatment. The proposed PEG[TKPF/mLMP2] vaccine efficiently delivers to dendritic cells (DCs) for activating T cell maturation, ultimately suppressing the growth of LMP2-expressing tumors in both prophylactic and therapeutic mouse models.

Our findings indicate a promising response rate associated with the combination of PD-1 antibody treatment and chemotherapy in pediatric patients with LELC, providing a theoretical basis for targeting DNA repair pathways. These outcomes suggest that clinical trials involving immune checkpoint inhibitors are warranted in pediatric patients with LELC.

P2/3, N=60, Not yet recruiting, SUNHO（China）BioPharmaceutical CO., Ltd.

The study highlights the under-expressed YAP1 and miR-340-5p in metastasis tumor cases, suggesting their potential role as a tumor suppressor in NPC.

P3, N=236, Active, not recruiting, Sun Yat-sen University | Trial completion date: Apr 2024 --> Apr 2025

P3, N=466, Not yet recruiting, Sun Yat-sen University

In conclusion, toripalimab plus anlotinib is well tolerated and shows promising efficacy in patients with RM-NPC, and ctDNA could be a potential predictive biomarker. The trial is registered at ClinicalTrials.gov (NCT04996758).

Our findings demonstrate SNHG14 plays a significant role in promoting chemoresistance of NPC cells to cisplatin through U2AF2/Notch2 axis. These results highlight potential therapeutic targets for NPC treatment.

ICI + Chemo confers superior survival benefits compared to chemotherapy in first-line RM-NPC treatment, independent of PD-L1 expression or other factors. However, ICIs alone demonstrate a manageable safety profile but do not surpass chemotherapy in efficacy for subsequent-line treatment.

Finally, we demonstrated the correlation and co-expression of LMP1-induced PARP1, HIF1A, HK2, and key glycolysis-related factors, further suggesting that LMP1 actively regulates the glycolysis pathway. Therefore, our study presents a comprehensive functional encyclopedia of the interactions between EBV antigens and host signaling pathways across various EBV-associated diseases, providing valuable insights for the development of therapeutic strategies.

The in vivo tumor targeting ability and imaging also showed that Z239-1907 specifically and selectively targeted NPC xenograft mice models and accumulate at tumor site as early as 30 min and disappeared within 24 h post-injection. Collectively, these results suggest that Z239-1907 dual-target affibody is a promising therapeutic agent and a molecular imaging probe for early diagnosis in NPC.

Our findings suggest that bromelain can target key proteins involved in NPC oncogenesis, with the strongest affinity towards PIK3CA. This suggests a hypothetical insight into bromelain's anticancer effects on NPC through the modulation of the PI3K/Akt signaling pathway.

P1, N=42, Active, not recruiting, Baylor College of Medicine | Recruiting --> Active, not recruiting | Trial primary completion date: Feb 2025 --> Jan 2024

Herein, we revealed a strong and direct link between AXL, cytokines in TIME, and MDSC differentiation and accumulation. Our work highlights novel approaches to optimizing existing immunotherapeutic interventions.

Consequently, CircINADL enhanced the stability of the HuR target gene Yes1-associated transcriptional regulator (YAP1), leading to the dysregulation of the Hippo signaling pathway. In conclusion, our study reveals the function of circINADL in promoting NPC metastasis and highlights its potential as a biomarker and therapeutic target for NPC treatment.

In conclusion, results from the present study suggest that ELF1 is overexpressed in GC. ELF1 combined with MMP9 can serve as a predictor of malignant biological behavior in GC and therefore a prognostic indicator for patients, due to its association with the tumor microenvironment.

ANXA6, negatively correlated with NPC development and metastasis, is a potential prognostic biomarker with tumor-suppressing effects. Multi-omics analysis highlights its clinical and immune regulatory roles, offering insights for future biomarker and molecular mechanism studies in NPC.

Copy number variation occurred in five genes, including PTEN, CCDN1, FGF19, FGF3 and FGF4. PTEN and fibroblast growth factors might be involved in the molecular regulation of brain metastasis in nasopharyngeal carcinoma.

P1/2, N=48, Active, not recruiting, National University Hospital, Singapore | Not yet recruiting --> Active, not recruiting | Trial completion date: Mar 2024 --> Jun 2025 | Trial primary completion date: Mar 2023 --> Jul 2024

Our study elucidates a novel mechanism where HNRNPH1 and METTL14 work together to maintain the stability of FLOT2 mRNA, thereby promoting NPC progression. Targeting this pathway presents a promising therapeutic strategy for the treatment of NPC.

P1/2, N=26, Active, not recruiting, Viracta Therapeutics, Inc. | N=130 --> 26

P2, N=98, Not yet recruiting, NRG Oncology | Trial completion date: Sep 2026 --> Jan 2027 | Initiation date: Oct 2024 --> Apr 2025 | Trial primary completion date: Sep 2026 --> Jan 2027

We demonstrated that FOXA1 prevents tumor immune evasion by inhibiting IFN-γ induced PD-L1 expression in NPC cells. Our research findings provide new insights into the immunotherapeutic biomarkers and targets for NPC, which is important for the clinical application of programmed cell death protein-1/PD-L1 antibodies in NPC.