Materiały źródłowe

• #1 Nasopharyngeal Carcinoma (NPC, Lymphoepithelioma) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558922/

  Nasopharyngeal carcinoma (NPC), previously known as lymphoepithelioma, is a malignancy arising from the epithelium of the nasopharynx. […] A complex interplay of genetic susceptibility and Epstein Barr virus (EBV) infection is responsible for the disease. […] An interplay of environmental factors, genetic structure, and EBV infection is involved in the etiology of the disease. […] EBV is highly associated with NPC. Many studies illustrate multiple processes and mechanisms that EBV can activate or inhibit in the host cell while transforming it into a cancer cell. EBV affects the cells by bringing its encoded-proteins or RNA molecules that affect host cells, and these molecules could be summarized but not restricted to: […] The development of nasopharyngeal carcinoma depends on multiple factors, such as genetic susceptibility, environmental factors, and infections such as Epstein-Barr virus (EPV) infection. Many studies linked multiple genes to the pathogenesis of the NPC; one of these genes is a region in human leukocyte antigen (HLA) genes at chromosome 6. Other genes have been identified in different locations on different chromosomes such as 13q12, 3q26, 5p15, 6p21, and 9p21.

• #2 The role of Epstein-Barr virus infection in the pathogenesis of nasopharyngeal carcinoma

  https://www.virosin.org/article/doi/10.1007/s12250-015-3592-5

  Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. EBV episomes are detected in almost all NPC cells. The role of EBV in NPC pathogenesis has long been postulated but remains enigmatic. In contrast to infection of B lymphocytes, EBV infection does not directly transform nasopharyngeal epithelial cells into proliferative clones with malignant potential. Genetic alterations in premalignant nasopharyngeal epithelium, in combination with inflammatory stimulation in the nasopharyngeal mucosa, presumably play essential roles in the establishment of a latent EBV infection in infected nasopharyngeal epithelial cells during the early development of NPC. Establishment of latent EBV infection in premalignant nasopharyngeal epithelial cells and expression of latent viral genes, including the BART transcripts and BART-encoded microRNAs, are crucial features of NPC. Expression of EBV genes may drive further malignant transformation of premalignant nasopharyngeal epithelial cells into cancer cells. The difficulties involved in the establishment of NPC cell lines and the progressive loss of EBV episomes in NPC cells propagated in culture strongly implicate the contribution of host stromal components to the growth of NPC cells in vivo and maintenance of EBV in infected NPC cells. Defining the growth advantages of EBV-infected NPC cells in vivo will lead to a better understanding of the contribution of EBV infection in NPC pathogenesis, and may lead to the identification of novel therapeutic targets for NPC treatment.

• #3 Carcinogenesis of nasopharyngeal carcinoma: an alternate hypothetical mechanism | Cancer Communications | Full Text

  https://cancercommun.biomedcentral.com/articles/10.1186/s40880-015-0068-9

  Current proposed mechanisms implicate both early and latent EpsteinBarr virus (EBV) infection in the carcinogenic cascade, whereas epidemiological studies have always associated nasopharyngeal carcinoma (NPC) with early childhood EBV infection and with chronic ear, nose, and sinus conditions. […] The EpsteinBarr virus (EBV) has been definitively implicated in the pathogenesis of NPC. […] We propose that there is a common genetic susceptibility in populations that are prone to NPC as a result of common ancestral origins, which in turn results in a tendency towards EBV chronic infection at an early age. Thereafter, the addition of some environmental insult (such as nitrosamines as previously proposed) results in the malignant transformation of the nasopharyngeal epithelium to NPC. […] Most NPC patients present with IgA antibodies to EBV viral capsid antigen (EBV-VCA) and EBV nuclear antigen 1 (EBNA1), and previous studies have shown that such IgA responses often precede tumor presentation by several years.

• #4 The role of Epstein-Barr virus infection in the pathogenesis of nasopharyngeal carcinoma

  https://www.virosin.org/article/doi/10.1007/s12250-015-3592-5

  The tumorigenic potential of EBV was first observed in Burkitt’s lymphoma, a special type of childhood cancer common among African children. In addition to Burkitt’s lymphoma, EBV infection was later observed in other human malignancies, including hematological and lymphatic tumours, such as Hodgkin’s disease, T cell lymphoma, and NK cell lymphoma, and epithelial cancers, such as nasopharyngeal and gastric carcinomas. In all cases, the nature of EBV infection in infected cancer cells is predominantly latent. […] Nasopharyngeal carcinoma (NPC) is unique in its close association (100%) with EBV infection. It is a rare cancer in Western countries, but a common cancer in the ethnic Chinese population living in the southern provinces of China. NPC is closely associated with Cantonese-speaking populations and is nicknamed „Cantonese cancer”. The etiology of NPC is multifactorial, and includes genetic predisposition, EBV infection, and diet. The major histological type of NPC in endemic regions is undifferentiated NPC, which is associated with EBV infection. EBV infection could be demonstrated in almost every NPC cell, distinguishing NPC from other squamous carcinomas arising in the head and neck regions, which are all EBV-negative. NPC patients have elevated serological IgA against the EBV lytic protein-viral capsid antigen (VCA) and early antigen (EA). The detection of IgA against EBV VCA and EBV DNA in plasma are important diagnostic tools of NPC, and are used extensively in early screening of NPC in high-risk populations.

• #5 Nasopharyngeal Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459256/

  The most potent risk factors for nasopharyngeal carcinoma development have been identified as major histocompatibility complex (MHC) I gene variants. […] The most widely accepted theory of tumorigenesis in EBV-related nasopharyngeal carcinoma (given EBV’s implication in various malignancies) suggests a clonal malignancy originating from a single, latently infected progenitor cell in the lymphocyte-rich nasopharyngeal mucosa. […] A hallmark of EBV-related nasopharyngeal carcinoma is the necessity for multiple genetic abnormalities induced by latent viral genes for oncogenesis. Specifically, EBNA, EBER1, and EBER2 have been extensively studied, with LMP1 emerging as a key oncoprotein. LMP1 is a potent signal activator for various pathways, including JNK/AP1, P13K, MAPK, and NF-B.

• #6 Pathogenesis and Etiology of Nasopharyngeal Carcinoma | SpringerLink

  https://link.springer.com/chapter/10.1007/174_2023_471

  Nasopharyngeal carcinoma (NPC) is an epithelial malignancy that originates from the nasopharynx, ubiquitously in the ostium of the Eustachian tube in the superior posterior wall of the nasopharynx (Sham et al. 1990). […] Despite sharing a tissue lineage with other mucosal head and neck cancers, NPC exhibits significant differences in its epidemiological distribution, pathogenic subtypes, etiologic factors, clinical features, and therapeutic approaches (Chen et al. 2019). […] It is characterized by the strong etiological and pathological association with Epstein-Barr virus (EBV) infection. […] The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC) is significant. […] Epstein-Barr virus infection and the pathogenesis of nasopharyngeal carcinoma: viral gene expression, tumour cell phenotype, and the role of the lymphoid stroma.

• #7 Pathogenesis and Etiology of Nasopharyngeal Carcinoma | SpringerLink

  https://link.springer.com/chapter/10.1007/174_2023_471

  The Epstein-Barr virus latent membrane protein 2A PY motif recruits WW domain-containing ubiquitin-protein ligases. […] The EBV nuclear antigen 1 (EBNA1) enhances B cell immortalization several thousandfold. […] The signaling pathways of Epstein-Barr virus-encoded latent membrane protein 2A (LMP2A) in latency and cancer. […] The pathological roles of BART miRNAs in nasopharyngeal carcinoma. […] The addition of pretreatment plasma Epstein-Barr virus DNA into the eighth edition of nasopharyngeal cancer TNM stage classification. […] The mechanism of Epstein-Barr virus infection in nasopharyngeal carcinoma cells. […] The expression and function of Epstein-Barr virus encoded latent genes. […] The role of Epstein-Barr virus infection in the pathogenesis of nasopharyngeal carcinoma.

• #8 Nasopharyngeal carcinoma: A review of current updates

  https://www.spandidos-publications.com/10.3892/etm.2018.5878

  The link between EBV and NPC was first proposed in 1966 when NPC patients were reported to have higher antibody response against an antigen that was later demonstrated as a product of EBV. […] Since then, extensive evidence suggests that EBV is a potential cause of NPC, especially type III. […] Elevated IgA antibodies against EBV antigens are highly specific markers for subsequent NPC in high-incidence areas, while elevated EBV-neutralizing antibodies blocking B-cell infection and anti-gp350 antibodies are inversely associated with NPC risk. […] The expression of viral proteins, such as latent membrane protein 1 (LMP1), LMP2, EBNA1 and EBNA2, has been demonstrated to drive tumor progression in invasive epithelial cancers. […] The household environment during childhood, when primary EBV infection is most probable, including number of siblings and population density of the household, could be important predictors for the immunological control of EBV and eventual EBV-related disease risk.

• #9 Nasopharyngeal carcinoma: A new synthesis of literature data (Review)

  https://www.spandidos-publications.com/10.3892/etm.2021.11059

  Nasopharyngeal carcinoma (NPC) is an epithelial tumor, which develops most frequently from the lateral pharyngeal recess and holds some complex epidemiological characteristics. […] Causal factors for NPC development include: tobacco, alcohol and nitrosamine-containing food consumption. Alcohol, especially when it is combined with tobacco, has an increasing effect as regards the risk of developing this type of cancer. […] A first step in NPC development is considered to be the stable infection with EBV in the nasopharyngeal epithelium. Similarly, at the epithelial cell level, EBV infection manifests through lithic replication; in NPC development, slow replication appears to be the dominant infective manner. […] One of the most studied oncoproteins is LMP1; it is considered to be the main EBV oncoprotein, which on the one hand can induce important genetic and epigenetic alterations, and on the other hand can promote cellular mobility, invasion and cervical lymph node metastasis, a unique characteristic of NPC.

• #10 Nasopharyngeal carcinoma: A new synthesis of literature data (Review)

  https://www.spandidos-publications.com/10.3892/etm.2021.11059

  In short, the oncogenic activity of EBV is revealed by the important effects exerted on the host genome, modifying its genetic profile, inducing genomic instability, evading host immunity and promoting cell survival through LMP1 activity. […] Inflammation is a key player in the cytokine release phenomena, and also in tumor development, progression and migration. Literature data suggests that malignant cells use chemokine gradients in order to metastasize to other body sites. Interleukin-6 (IL-6) appears to have a role in NPC progression, as it has the capacity of promoting malignant behavior. […] NPC develops from the surface of crypt epithelium found in the mucous layer of the nasopharynx. […] The therapeutic approach of NPC should be personalized for each patient, according to some factors such as the time of diagnosis (early or late diagnosis), tumor stage, tumor grade and histopathology type, depth of tumor invasion, performance status, local expertise availability, the general health state of patients, associated pathology, and preferences. […] NPC was determined to also be sensitive to chemotherapy, and radiotherapy sensitivity is correlated highly with chemotherapy sensitivity. The standard of care in locally and regionally advanced cases of NPC is concomitant platinum-based chemotherapy.

• #11 Precision medicine in nasopharyngeal carcinoma: comprehensive review of past, present, and future prospect | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04673-8

  NPC carcinogenesis comprises a complex process of genetic and epigenetic alterations which are driven by diverse oncogenic molecular events. For example, oncogenic DNA methylation, histone modification, abnormal activation or miRNAs/lncRNAs silencing are the epigenetic mechanisms that are involved in NPC pathogenesis. Besides that, hyperactivation of cellular signalling pathways such as prosurvival pathways, PI3K/Akt, NF-B, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription (STAT) 3, Wingless-related integration site (Wnt)/-catenin] and abnormal negative regulation of proapoptosis pathways (p53, endoplasmic reticulum stress), and tumor necrosis factor (TNF) signalling pathway are associated with NPC pathogenesis. EBV infection is usually the main driver of these molecular alteration in non-keratinizing NPC. Different molecular aberrations across the individual has led to different response towards similar treatment. Therefore, specifically targeting certain aberrant molecules that participate in NPC tumorigenesis could potentially improve the treatment response.

• #12 Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-020-00340-2

  Mutations and repair disorders caused by viral infection are important causes of malignant changes in the nasopharyngeal epithelium. […] The epigenetic machinery of NPC cells could be altered to reprogram the epigenomes of virus and host cells through EBV-encoded proteins. […] The promoter hypermethylation of RASSF1A, BLU, CDKN2A, and DLEC1 could be detected in NPC, which have roles in DNA damage response, stress response, cell proliferation during G1 and STAT3 signal pathway. […] Targeted therapy involves the design of specific drugs that bind specifically to oncogenic targets within tumor cells to inhibit the development of tumors. […] In addition, abnormal activation and silencing of signal pathways in tumor cells also have a crucial role in tumor activities. […] Imbalance of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signal pathway is associated with malignant transformation and apoptosis of tumor cells, and metastasis and radioresistance of tumor tissues.

• #13 Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-020-00340-2

  The activation of the PI3K/Akt pathway is also related to EBV-encoded latent membrane proteins 1, 2A, 2B. […] The activation of the PI3K/Akt pathway is also related to EBV-encoded latent membrane proteins 1, 2A, 2B. […] The NF-B pathway can also be combined with immunotherapy. […] The NF-B pathway can also be combined with immunotherapy. […] The targeted inhibition of p65, LMP1, IKK, CDH6, Pim1, BST2, NEAT1, and the targeted activation of SIRT6, DLC-1, TNFAIP3, RERG, NKG2DLs in the targeted therapy of NPC could be a potential therapeutic strategy through the NF-B pathway. […] The targeted inhibition of MAP2K6, PAK1, MNK1, FGF2, PIN1, PBK, and the targeted activation of DAPK1, BLU, miR-124 in the targeted therapy of NPC could be a potential therapeutic strategy through the MAPK pathway.

• #14 Feature Reviews of the Molecular Mechanisms of Nasopharyngeal Carcinoma

  https://www.mdpi.com/2227-9059/11/6/1528

  It is likely that genetic aberrations, environmental factors, and EBV infection cooperate in NPC tumorigenesis, during which cellular signaling pathways are often altered. Clarifying how these oncogenic pathways contribute to NPC can potentially help us find new druggable targets. Based on GWAS, mutations in NPC can be categorized into the following pathways: Dysregulation of NF-κB, which is important for angiogenic and tumorigenic regulation, is often observed in cancer. The constitutive activation of NF-κB is associated with the dysregulation of the transcription of genes that encode cytokines, chemokines, adhesion factors, and inhibitors of apoptosis. By EMSA, Western blotting, and immunohistochemical staining, constitutive activation of NF-κB complexes, either p50/p50/Bcl3 or p50/RelB, was found in almost all EBV-positive NPC tumors and cell lines. More recently, GWAS have shown that dysregulation of the NF-κB signaling pathway is caused by various somatic alterations in genes encoding members of this pathway. Multiple truncating mutations in three negative regulators, including NF-κB inhibitor alpha (NFKBIA), cylindromatosis (CYLD), and TNF alpha-induced protein 3 (TNFAIP3), were found in NPC primary tumors in a whole-exome study at a high frequency. NFKBIA regulates NF-κB nuclear translocation. CYLD encodes deubiquitinating enzymes (DUBs), which regulate cell growth and invasiveness by untying K63-linked ubiquitin chains through deubiquitination. TNFAIP3, the gene encoding A20, is associated with a wide panel of inflammatory pathologies. Mutations in these negative regulators can lead to constitutive activation of the NF-κB pathway in NPC. It has also been demonstrated that in the majority of NPCs examined, EBV-encoded LMP1 expression underpins constitutive NF-κB activation, which contributes to inflammatory and immune escape.

• #15 The role of long noncoding RNA-LET in cell proliferation and invasion | OTT

  https://www.dovepress.com/the-role-of-long-noncoding-rna-let-in-cell-proliferation-and-invasion–peer-reviewed-fulltext-article-OTT

  Our results show that LET exerts a significant antitumor effect via the regulation of the proliferation, adhesion, invasion and cell cycle of NPC. […] Our study also showed that overexpressing LET could inhibit the phosphorylation of ERK1/2, while silencing of LET could promote its activation. […] Collectively, all these results suggest that lncRNA-LET could effectively regulate the cell proliferation, adhesion and invasion of NPC. This is the first report to fully demonstrate its potential anticancer effect in NPC cells, and the results may provide a theoretical support for its application in clinical treatment of NPC.

• #16 Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-020-00340-2

  For STAT3 pathways, except for directly targeting STAT3 for NPC treatment, targeted inhibition of LMP1, AP1, LncRNA DANCR, and targeted activation of miR-29a, miR-124-3p, and RKIP may become potential treatment strategies for NPC. […] The targeted inhibition of -catenin, Capn4, CBP, LHX2, FOXO3a, and the targeted activation of GSK3 in the targeted therapy of NPC could be a potential therapeutic strategy through the Wnt/-catenin pathway.

• #17 Genetic and epigenetic landscape of nasopharyngeal carcinoma – Dai – Chinese Clinical Oncology

  https://cco.amegroups.org/article/view/9478/html

  Nasopharyngeal carcinoma (NPC) is a unique epithelial malignancy that shows a remarkable geographical and ethic distribution. Multiple factors including predisposing genetic factors, environmental carcinogens, and Epstein-Barr virus (EBV) infection contribute to the accumulation of genetic and epigenetic alterations leading to NPC development. […] Genome-wide studies show that typically NPC tumors are characterized as having comparatively low mutation rates, widespread hypermethylation, and frequent copy number alterations and chromosome abnormalities. […] This model proposes a critical role of the genetic and epigenetic factors in the pathogenesis of NPC. […] Previous studies suggested that there are several cofactors that are associated with NPC development. They are the dietary factors, infection with an oncovirus, Epstein-Barr virus (EBV), and genetic predisposition. NPC is associated with genetic alterations on particular chromosomal regions and genes, harboring of specific cancer-associating single nucleotide polymorphisms (SNPs), and familial aggregation. Interestingly, recent studies confirm that epigenetic alterations, including the promoter hypermethylation, are also one of the crucial factors that are highly associated with NPC.

• #18 Genetic and epigenetic landscape of nasopharyngeal carcinoma – Dai – Chinese Clinical Oncology

  https://cco.amegroups.org/article/view/9478/html

  Aberrant epigenetic alterations, particularly DNA methylation, have been frequently reported in NPC. […] A number of tumor suppressors were found to be downregulated by promoter methylation. Aberrant methylation of tumor suppressors RASSF1 and CDKN2A was considered as important early events in NPC tumorigenesis. […] These results emphasize the importance of integrating the genetic and epigenetic changes to provide a comprehensive view of molecular changes in NPC. […] In NPC, EBV is harbored in a latent stage with restricted viral gene expression of LMP1/2, EBNA1, EBER1/2, and BARTs. LMP1 can activate cellular DNA methyltransferase via c-Jun NH2-terminal kinase signaling and upregulate BMI1 expression, which is associated with epigenetic changes in NPC. […] Although the high-throughput characterization methods, such as massive parallel sequencing, SNP, and methylation assays, has resulted in a greater understanding of NPC biology, yet much remains to be uncovered.

• #19 Identifying Key Genes for Nasopharyngeal Carcinoma by Prioritized Consensus Differentially Expressed Genes Caused by Aberrant Methylation

  https://www.jcancer.org/v12p0874.htm

  Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated epithelial malignancy. […] NPC pathogenesis has been reported to be strongly associated with multiple factors, including host genetics, viral infection, and environmental effects, which can result in genetic and epigenetic alternations. […] Aberrant epigenetic alterations such as DNA methylation can disrupt or over-activate critical signaling pathways. Compared with other cancer types, such as liver, head and neck, colon, lung, thyroid, kidney, breast, pancreatic, and prostate cancers, NPC has a higher hypermethylation frequency. […] Genes downregulated by promoter hypermethylation could represent biomarkers for disease progression and prognosis in NPC. […] Through integrated analysis of DNA methylation and mRNA and miRNA expression profiles, we prioritized 56 hypermethylated downregulated genes, including 7 tumor suppressor genes, and constructed a miRNA-target regulation network consisting of 12 hypermethylated miRNAs and 25 upregulated oncogenes.

• #20 Nasopharyngeal Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459256/

  Nasopharyngeal carcinoma stands out as a distinct subtype of head and neck cancer with a pathogenesis that is equally unique. Most nasopharyngeal carcinoma cases are EBV-related, and research regarding pathogenesis and malignant transformation in nasopharyngeal carcinoma has focused on various viral gene products, along with host genetic factors that may increase susceptibility to EBV infection. […] In endemic areas, the majority of nasopharyngeal carcinoma tumor cells and precancerous lesions have been found to contain isolated EBV DNA, reinforcing causative association. Additionally, a strong correlation exists with human leukocyte antigen (HLA) mutations that increase susceptibility to malignant transformation, and these mutations are more prevalent among individuals of Chinese and other Southeast Asian ancestries.

• #21 Nasopharyngeal Cancer and the Southeast Asian Patient | AAFP

  https://www.aafp.org/pubs/afp/issues/2001/0501/p1776.html

  Epstein-Barr virus, a herpesvirus, is the causative agent in acute infectious mononucleosis and is also associated with Hodgkin’s disease, Burkitt’s lymphoma, lymphoproliferative disease in the post-transplant setting, and T-cell lymphoma. The link between nasopharyngeal cancer and Epstein-Barr virus was first observed in 1966, when the sera of patients with the malignancy were found to manifest precipitating antibodies against cells infected with the virus. […] Genetic susceptibility has also been proposed as a risk factor for the development of nasopharyngeal cancer. Haplotypes that have been associated with the malignancy include certain human leukocyte antigens (HLA), including HLA-A2, HLA-B46 and HLA-B58.

• #22 Nasopharyngeal carcinoma: A review of current updates

  https://www.spandidos-publications.com/10.3892/etm.2018.5878

  Hence, we hypothesized that very early exposure to EBV and other carcinogens may play a role in NPC pathogenesis. […] Familial clustering has been consistently reported in NPC high-incidence, intermediate-incidence, and low-incidence areas. […] This magnitude of association is among the highest of any malignancy, suggesting that environmental factors themselves cannot fully explain the observed association. […] An inheritance pattern that cannot be explained by activation of a single major susceptibility gene is supported by results from a complex segregation analysis of familial NPC showing that the etiology of NPC involves interaction of multiple genetic and environmental factors. […] Only one genome-wide association study (GWAS) utilized samples from 1,000 cases and controls; other GWAS were limited to a few hundred cases and controls.

• #23 The role of Exosomes in the Pathogenesis of Nasopharyngeal Carcinoma and the involved Clinical Application

  https://www.ijbs.com/v17p2147.htm

  Exosomes can mediate continuous interference between cancer cells and stromal cells and the effect becomes stronger under hypoxic conditions. […] The salient feature of NPC is the infiltration of a large number of non-malignant white blood cells in the primary tumor, mainly consisting of T lymphocytes and a small number of B cells, macrophages and dendritic cells, etc. […] However, this leukocyte infiltration has been found to disappear in the process of metastasis, replaced by rapidly and massively proliferated malignant cells with obvious anti-tumor immune feature. […] Exosomes can arouse radioresistance by enhancing intercellular communication and cytotoxic damage in NPC cells. […] NPC patients also develop resistance to drugs, where exosomes may be the transmitter. […] Exosomes can provide protection for their contents against proteolytic digestion or drug action, which may be one of the causes for the failure of drug effect on NPC treatment, as exosomal cancer-promoting molecules move from the cancerous cells to the recipient cells.

• #24 Metastasis of nasopharyngeal carcinoma: What we know and do not know | Visualized Cancer Medicine

  https://vcm.edpsciences.org/articles/vcm/full_html/2021/01/vcm20200018/vcm20200018.html

  The overexpression of EBERs can trigger the secretion of pro-inflammatory cytokines, macrophage colony-stimulating factor (M-CSF), and monocyte chemo-attractant protein (MCP-1) via nuclear factor-B (NF-B) and IRF3 signaling pathways to form a pro-tumorigenic inflammatory tumor microenvironment, which consequently promotes NPC development. […] Taken together, the EBV infection is an important factor in promoting NPC cellular motility and metastasis from multiple angles and involves multiple signaling pathways. […] Multiple cytokines are NPC metastasis promoters. These secreted molecules commonly act through both autocrine and paracrine manners in promoting NPC metastasis. […] Other cytokines reported to promote NPC cellular motility in vitro, and hence are potential NPC metastasis-promoters, include TNFAIP2, IL-6, and IL-17A. […] In recent years, several NPC metastatic inhibitors have been revealed acting through a variety of mechanisms illustrating the complexity of NPC metastasis.

• #25 Carcinogenesis of nasopharyngeal carcinoma: an alternate hypothetical mechanism | Cancer Communications | Full Text

  https://cancercommun.biomedcentral.com/articles/10.1186/s40880-015-0068-9

  We postulate that NPC carcinogenesis follows a similar model. Neonatal transmission of EBV infects the nasopharyngeal epithelium with resultant latency in the basal epithelium (salivary gland cells) during the developmental period of the transformational zone. Entry of the virus into the epithelial cells may perhaps be mediated in this case by integrin 6. Exposure to subsequent carcinogenic insults triggers the carcinogenic cascade that takes years for the eventual malignant transformation to NPC.

• #26 Thoughts on Beta-integrins and a postulated pathogenesis for nasopharyngeal carcinoma – Poh – Annals of Nasopharynx Cancer

  https://anpc.amegroups.org/article/view/4318

  The Epstein-Barr virus (EBV) has been definitively implicated in the development of nasopharyngeal cancer (NPC). […] The current dogma regarding EBV infection in NPC has been that of late infection, followed by multiple postulated mechanisms for immune evasion of EBV against the host defences, leading to eventual trigger of carcinogenesis. […] This paper postulates that beta-integrin 6, which is primarily expressed during embryonic development and possibly in neonatal life, may play a role in the development of NPC by facilitating entry of EBV into cells within the nasopharynx during the perinatal period, and this, coupled with ethnic differences in cell-mediated and innate immunity, leads to latent infection within the nasopharynx. […] Subsequent accumulation of further environmental and/or oncogenic changes leads to the eventual development of NPC in the patient in later life.

• #27 The role and mechanism of aerobic glycolysis in nasopharyngeal carcinoma [PeerJ]

  https://peerj.com/articles/19213/

  The review underscores aerobic glycolysis as a cancer hallmark, particularly amplified in nasopharyngeal carcinoma, affecting processes like invasion and metastasis. […] It details the regulatory functions of four key enzymes (hexokinase 2, lactate dehydrogenase A, phosphofructokinase 1, and pyruvate kinase M2) that influence tumor progression through pathways like PI3K/Akt and mTOR. […] The review suggests that targeting components of aerobic glycolysis could enhance treatment precision and reduce side effects. […] Aerobic glycolysis, a novel hallmark of NPC, is believed to promote NPC induction of immune evasion, growth, and proliferation through several mechanisms: (a) Overexpression of key glycolytic enzymes and glucose transporters, accelerated glycolytic fluxes, and the subsequent accumulation of glycolytic intermediates that are diverted to biomass synthesis in nasopharyngeal carcinoma cells.

• #28 The role and mechanism of aerobic glycolysis in nasopharyngeal carcinoma [PeerJ]

  https://peerj.com/articles/19213/

  (b) ATP is generated at a high rate through aerobic glycolysis to meet the increased energy requirements of cancer cells, allowing tumors to adapt to their energy-deficient microenvironment. […] (c) accumulation of high levels of lactate drives tumor progression. […] Consequently, aerobic glycolysis is closely related to cancer. […] The relationship with nasopharyngeal carcinoma has become a research focus in recent years and has attracted extensive academic attention. […] The mTOR signaling pathway has been shown to be intimately associated with glycolytic enzymes. […] The hallmark difference between cancer cells and normal cells is metabolic reprogramming, and aerobic glycolysis is considered to be the major metabolic phenotype in cancer. […] The aberrant activation of signaling pathways can lead to a myriad of human diseases.

• #29 Emerging roles of lncRNA in Nasopharyngeal Carcinoma and therapeutic opportunities

  https://www.ijbs.com/v18p2714.htm

  Nasopharyngeal carcinoma (NPC) is a kind of malignant tumor with ethnic and geographical distribution characteristics. However, the molecular mechanisms of NPC are still unclear. Long non coding RNAs (lncRNAs) are becoming important regulators in gene expression networks, including post transcriptional and post translational regulation of protein, protein complex organization, signal transduction and recombination among cells, which are involved in cancer recognition. Recent evidence shows that lncRNAs play important roles in the occurrence and development of NPC. Therefore, in-depth understanding of abnormal lncRNAs will provide new understanding of the pathogenesis in NPC, and provide new tools for the early diagnosis and treatment of NPC. This article reviews the abnormal lncRNAs in NPC cells and the roles of lncRNAs in the tumorigenesis of NPC.

• #30 Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258187

  Meta-analysis identified activation of lipopolysaccharide (LPS)-induced tissue injury in NPC tissue. […] Our analysis illustrates that nasal epithelial barrier dysregulation and maladaptive immune responses are key components of NPC pathogenesis along with LPS-induced tissue damage. […] Further studies are required to better understand molecular mechanisms involved in NPC pathophysiology, such as the roles of lipopolysaccharide (LPS) and general inflammation on nasopharyngeal tissue injury, HOXA10 and matrix metalloproteinases 1 and 3 (MMP1, MMP3) pathways. […] It has been hypothesized that LPS could be a leading driver and inducer of tumorigenesis of NPC, possibly through inflammation. […] IPA identified lipopolysaccharide (LPS)-induced tissue injury as the top upstream regulator (p = 3.03E-14, activation Z-score = 4.507).

• #31 Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258187

  Inflammation has long been known to be associated with tumorigenesis either as a response to tumor growth or a driver. […] Specifically, multiple theories exist regarding LPS-induced inflammation and NPC oncogenesis, one of which involving repression of a protective gene; the short palate, lung and nasal epithelium clone 1 (SPLUNC1). […] Thus, LPS-containing gram negative bacteria are thought to stimulate TLR4-dependent inflammation by resident macrophages, resulting in the secretion of cytokines (such as TNF and IL-1), which irritates the mucosa and induces MAPK-mediated cellular proliferation and tumorigenesis. […] Our analysis suggests that etanercept is known to lead to changes of expression in genes that were found to differentiate NPC tissue from normal epithelium.

• #32 The Pathogenesis and Therapeutics of Nasopharyngeal Carcinoma

  https://www.itmedicalteam.pl/articles/the-pathogenesis-and-therapeutics-of-nasopharyngeal-carcinoma-106094.html

  Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma and arises from nasopharynx epithelium, with a geographical and racial distribution. NPC has been demonstrated to be strongly associated with environmental factors, genetic susceptibility and viral infection, especially EpsteinBarr virus (EBV) infection. […] NPC initiation and progression is strongly associated with genetic susceptibility and viral infection, besides environmental factors. […] It has been documented that NPC development is strongly associated with three key etiological factors, including environmental factors such as chemical carcinogens and toxic pollutants, genetic susceptibility and viral infection, particularly, EBV infection. […] Viral infection, particularly EpsteinBarr virus (EBV) infection, has been demonstrated to be a critical etiological factor in NPC pathogenesis. EBV infection are particularly connected with the non-keratinizing types II and III NPC, which account for more than 95% of all NPC cases in Southern China, with the absence of EBV infection in type I NPC cases. […] High risky EBV variants characterized by distinct polymorphisms in the EBER locus are reported to have a strong association with NPC. […] EBV reactivation changed the balance between EBV and host body and induced NPC pathogenesis. […] EBV plays critical roles in NPV development.

• #33 Nasopharyngeal carcinoma: molecular pathogenesis and therapeutic developments | Expert Reviews in Molecular Medicine | Cambridge Core

  https://www.cambridge.org/core/journals/expert-reviews-in-molecular-medicine/article/nasopharyngeal-carcinoma-molecular-pathogenesis-and-therapeutic-developments/F84CD27189FE4E7FED9FD634EA557059

  Nasopharyngeal carcinoma (NPC) is a prevalent tumour in southern China and southeast Asia, particularly in the Cantonese population, where its incidence has remained high for decades. Recent studies have demonstrated that the aetiology of NPC is complex, involving multiple factors including genetic susceptibility, infection with the EpsteinBarr virus (EBV) and exposure to chemical carcinogens. […] During development of the disease, viral infection and multiple somatic genetic and epigenetic changes synergistically disrupt normal cell function, thus contributing to NPC pathogenesis. […] New biomarkers for NPC, including EBV DNA copy number or methylation of multiple tumour suppressor genes, which can be detected in serum and nasopharyngeal brushings, have been developed for the molecular diagnosis of this tumour. […] Meanwhile, new therapeutic strategies such as intensity-modulated radiation therapy and immuno- and epigenetic therapies might lead to more specific and effective treatments.

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