Clinical utility of Epstein-Barr virus DNA and other liquid biopsy markers in nasopharyngeal carcinoma

Nasopharyngeal carcinoma(NPC)is a malignant epithelial tumor ubiquitously associated with the Epstein-Barr virus(EBV),which is highly prevalent in South China,Southeast Asia,and North Africa.Despite being a highly radio-sensitive and treatable cancer,a majority of NPC patients are diagnosed in their advanced stage,and locoregional and distant relapses following definitive treatment contribute largely to cancer-specific mortality among these patients.Given that EBV-driven NPC is the predominant variant seen in endemic regions,various EBV detection methods have been developed and are utilized in screening,prognostication,and post-treatment surveillance of NPC patients.While the Immunoglobulin A(IgA)serology assay is the most extensively studied EBV detection method,the detection of plasma EBV DNA released during replication or cellular apoptosis has shown superior outcomes in endemic population screening,prognostication,and detection of distant relapse.Furthermore,there is emerging evidence on the use of circulating tumor cells,microRNAs,DNA hypermethylation,and combination assays in various clinical scenarios.Herein,this paper provides a comprehensive overview of the relevant studies using various EBV detection techniques in the management of NPC.Specifically,the recent advances,clinical evidence,and challenges associated with the clinical application of EBV liquid biopsies in population screening,prognostication,and surveillance of NPC are presented.

Retreatment in locally recurrent nasopharyngeal carcinoma:Current status and perspectives

1 Background Nasopharyngeal carcinoma(NPC)arises from the epithelial cells that cover and line the nasopharynx.While it is considered a rare cancer globally,it is commonly observed in South China and a few other ethnically distinct racial groups.Due to its propensity to spread early through the submucosal tissue and the highly infiltrative nature of this disease,NPC spreads easily through areas of lesser resistance within the pharyngobasilar fascia with a tendency for neural infiltration[1-3].

Pan-CDK inhibition augments cisplatin lethality in nasopharyngeal carcinoma cell lines and xenograft models

In addition to their canonical roles in regulating cell cycle transition and transcription,cyclin-dependent kinases(CDKs)have been shown to coordinate DNA damage response pathways,suggesting a rational pairing of CDK inhibitors with genotoxic chemotherapeutic agents in the treatment of human malignancies.Here,we report that roniciclib(BAY1000394),a potent pan-CDK inhibitor,displays promising anti-neoplastic activity as a single agent and potentiates cisplatin lethality in preclinical nasopharyngeal carcinoma(NPC)models.Proliferation of the NPC cell lines HONE-1,CNE-2,C666-1,and HK-1 was effectively curbed by roniciclib treatment,with IC_(50)values between 11 and 38 nmol/L.These anticancer effects were mediated by pleiotropic mechanisms consistent with successful blockade of cell cycle CDKs 1,2,3,and 4 and transcriptional CDKs 7 and 9,ultimately resulting in arrest at G1/S and G2/M,downregulation of the transcriptional apparatus,and repression of anti-apoptotic proteins.Considerably enhanced tumor cell apoptosis was achieved following combined treatment with 10 nmol/L roniciclib and 2.0μmol/L cisplatin;this combination therapy achieved a response over 250%greater than either drug alone.Although roniciclib chemosensitized NPC cells to cisplatin,it did not sensitize untransformed(NP69)cells.The administration of 0.5 mg/kg roniciclib to BALB/c xenograft mice was well tolerated and effectively restrained tumor growth comparable to treatment with 6 mg/kg cisplatin,whereas combining these two agents produced far greater tumor suppression than either of the monotherapies.In summary,these data demonstrate that roniciclib has strong anti-NPC activity and synergizes with cisplatin chemotherapy at clinically relevant doses,thus justifying further evaluation of this combinatorial approach in clinical settings.

Real time in-vivo miniature endoscopic surveillance system for imaging of nasopharynx

Objective:To test the feasibility of a real time miniature endoscope system for imaging the nasopharynx.Study design:Preclinical assessment on skull model and cadaver.Methods:A 3.5 mm miniature endoscope was fabricated and the image capture of the nasopharynx was investigated by positioning the miniature camera system at the posterior free edge of the vomer bone.Wireless real time transmission of the images and quality was tested in a skull model.Next,three nasopharyngeal surveillance miniature camera system were developed for possible clinical translation.Two prototypes were anchored on the nasal septum and the last prototype was designed using a patient self-administered surveillance process.These prototypes were tested for feasibility on both the phantom skull and cadaveric model.Risk assessments were also performed to assess risk,safety and validate the reliability of the material utilized for clinical translation.Results:Insertion and anchorage of the miniature surveillance endoscope prototypes at the vomer bone were feasible on all 3 prototypes.The quality of captured images was reasonable and miniaturized camera was responsive to pan at different angles so that the entire nasopharynx may be surveyed.Risk assessments on the material such as pull out test,breaking force analysis,finite element test and tensile strength test were reliable for possible clinical translation.Conclusions:Real time miniature endoscope system for surveillance of nasopharyngeal cancer is feasible.Clinical translation of this technology was possible but requires further refinement in enhancing image quality and wireless transmission of the captured images.