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Role of Genetic Pathways in Nasopharyngeal Carcinoma
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This entry is adapted from the peer-reviewed paper 10.3390/genes12111835

Arrays of genes and molecular mechanisms underlie the development of chemoradiation resistance in NPC. Imperatively, unravelling the true pathogenesis of chemoradiation resistance is crucial as these significant proteins and genes can be modulated to produce an effective therapeutic target.

radiation resistance locoregional recurrence genetic alteration

1. Introduction

There are multiple critical mechanisms that underlie the chemoradiation resistance in NPC. This involves arrays of genes, proteins, and peptide products, which interact in a delicate system that play critical roles in modulation of the chemoradiation effects [1]. The comprehensive studies of genes and proteins are based on the fact that multiple genes can interact with signaling pathways to regulate radiosensitivity, and selected gene fusion can induce chemoradiation resistance. The activation of oncogenes or the loss of tumor suppressors plays important roles in tumor initiation and progression, which can also regulate the EMT process, CSC formation, and radiosensitivity of NPCs. All of these factors act in a cohesive ecosystem in inducing chemoradiation resistance in NPC.

2. Epithelial–Mesenchymal Transition (EMT)

Epithelial–mesenchymal transition (EMT) is a process by which cells change their original epithelial morphology, i.e., the epithelial cells transform into mesenchymal cells. The EMT has significant roles in cancer progression and metastases [2]. EMT allows solid tumors to become more malignant and invasive and have more metastatic potential. Recently, compelling evidence indicated that EMT transition in tumor cells also contributes to other malignant behaviors, such as chemoresistance and radioresistance [3].
Many facets of critical tumor growth are aided by EMT functions. Some chemo-resistant NPC cells have EMT features, implying that EMT is a type of chemo-resistance maintenance mechanism in NPCs. In NPC, Zhang et al. discovered a link between EMT and cisplatin resistance. They discovered that cisplatin-resistant NPC cells had more EMT characteristics, such as decreased E-cadherin expression and increased vimentin, fibronectin, and matrix metalloproteinase expression [4].

3. Carnitine Palmitoyl Transferase 1A (CPT1A)

Carnitine Palmitoyl Transferase 1A is a rate-limiting enzyme for mitochondrial fatty acid transportation, which plays a critical role in increasing fatty acid oxidation required for the cellular fuel demands. High expression of CPT1A promotes radiation resistance in NPC cells and contributes to poor overall survival of NPC patients following radiation therapy [5]. Disruption of CPT1A decreases radiation resistance by activating mitochondrial apoptosis both in vitro and in vivo [6]. Current research highlights the true mechanisms of CPT1A involvement in lipid reprogramming and this may serve as a new platform for the development of molecular-targeted treatment in order to improve the therapeutic effects of radiation in NPC.
The reprogramming of lipid metabolism is a relatively emerging characteristic of cancer. Increased lipid uptake, storage, and lipogenesis are all linked to fast tumor growth in a variety of malignancies. The sterol regulatory element-binding proteins (SREBPs) are a family of membrane-bound transcription factors found in the endoplasmic reticulum that play a key role in lipid metabolic control [7]. SREBPs are substantially upregulated in many malignancies and promote tumor growth, according to recent research. Importantly, SREBPs are interesting therapeutic targets since inhibiting them genetically or with pharmacological treatments greatly reduces tumor development and triggers cancer cell death. However, directly blocking SREBPs, on the other hand, is difficult because transcription factors are notoriously difficult to target with drugs. Inhibiting SREBP translocation from the ER to the Golgi is a more promising strategy. Fatostatin, betulin, and PF-429242 have been proven in pre-clinical tests to suppress SREBP activation and have promising anti-tumor properties [7].

4. RARS-MAD1L1 Fusion Gene

The chromosome translocations and relevant gene fusions may contribute to tumor progression, but also the fusion protein produced by a fusion gene can be oncogenic [8]. An example of this fusion gene includes RARS-MAD1L1, which can be found in primary NPC and induces cellular proliferation and stem cell properties in NPC [9]. The human far upstream element (FUSE) binding protein 1 was activated by RARS-MAD1L1 and was associated with poor survival in esophageal carcinoma [10]. Other examples include the FGFR3-TACC3 fusion gene, which promotes cell proliferation, colony formation, and transforming potential via activating the ERK and AKT signaling pathways.

5. Base Excision Repair (BER) Pathway

The base excision repair (BER) pathway has been identified as a predictor of therapeutic response, prognostic factor, and therapeutic target in a variety of cancers. The BER pathway is made up of a variety of glycosylases, endonucleases, polymerases, and ligases that work together to repair damaged DNA bases. Cancer cells take advantage of BER’s ability to repair DNA damage in order to resist DNA-damaging chemotherapies and radiotherapy. BER proteins have thus been identified as potential therapeutic targets and chemoresistance factors in a variety of cancers [11].
Base excision repair (BER) pathway is the main way to repair the radiation-induced DNA single-strand break, including the apurinic/apyrimidinic (AP) site break and DNA base injury. In a study by Wang et al., three genes, XRCC1, OGG1, and APEX1, in the BER pathway were studied in 174 NPC patients who were treated with chemoradiation with five potentially functional single nucleotide polymorphisms (SNPs). They reported that that XRCC1 and OGG1 had a significant impact on primary tumor efficacy at the end of radiotherapy [12], which may have effects on the chemoradiation resistance.

6. Bone Marrow Stromal Cell Antigen 2 (BST2) and NF-κB Pathway

BST2 was identified as a platinum-resistant factor in NPC patients. The upregulation of BST2 resulted in platinum resistance by activating the NF-κB pathway to promote the expression of anti-apoptotic proteins. It has been shown that BST2 upregulation was associated with poor survival in patients with locally advanced NPC [13]. NF-κB deregulation, either via somatic genetic events or LMP1 overexpression, is another core feature of NPC [14][15]. Abnormal NF-κB signaling and genetic mutations in NF-κB signaling-associated factors impact the tumorigenicity, proliferation, chemoresistance, and radioresistance of multiple kinds of cancers including NPC [8]. Normally, a variety of stimuli can initiate NF-κB signaling, such as cytokines, growth factors, reactive oxygen species, and ionizing radiation [16].

7. Endoplasmic Reticulum (ER) Stress Pathway

ER stress may be activated by tumor microenvironment factors such as hypoxia, pH changes, and oxidative stress induced by chemoradiation, which results in cancer and metastases. Functional polymorphisms in ER stress pathway-related genes, especially SNPs in the coding regions, may affect the expression and activity of proteins, which might be predictive factors for chemoradiotherapy efficacy and may account for the inter-patient response heterogeneity and chemoradiation resistance [17].

8. Wnt/β-Catenin Pathway

Activation of Wnt-β catenin pathway has been associated with tumorigenesis and cancer progression in various types of cancers. Wnt/β-catenin signaling pathway maintains the capability for self-renewal and differentiation and induces radioresistance in several human cancers including NPC [18][19]. Elucidation of the molecular details of the oncogenic activation of Wnt/β-catenin signaling may, therefore, lead to more effective treatments for patients with NPC [19].
β-catenin may play a role in the migration and proliferation of NPC cells. The SNPs were correlated with grade 3 radiation-induced toxic reactions in NPC patients [20]. This shows that the accumulation of β-catenin could promote the proliferation of NPC cells and weaken the efficacy of radiation.

9. Long Noncoding RNAs (lncRNAs)

Long noncoding RNAs (lncRNAs) are generally primary non-protein-coding sequences greater than 200 nucleotides in length. They can interact with DNA, RNA, and proteins [21]. They are a novel class of mRNA-like transcripts that have been shown to be involved in the development and progression of multiple cancers. The lncRNAs regulate many hallmarks of cancer, such as the malignant phenotype, by regulation of the epithelial-to-mesenchymal transition process (EMT), and influence cancer invasion and metastasis [22].
They also underlie the chemoradioresistance in NPC. Furthermore, multiple lncRNAs are abnormally expressed in cancer cells and have been linked to the establishment of cancer cells’ radioresistant character. Increasing evidence suggests that lncRNAs affect the transcription of genes involved in the DNA damage response via a variety of regulatory mechanisms [21]. Studies analyzing large clinical cancer samples demonstrated that certain lncRNAs serve as valuable prognostic biomarkers [23][24].

10. Tyrosine-Protein Phosphatase (SHP-1)—CK2 Inhibitor

Protein Kinase (CK2) is an important kinase expressed in most eukaryotes. The CK2 complex is a tetramer composed of two catalytic subunits, which play a vital role in cell growth, proliferation, differentiation, and apoptosis and are considered to be potential targets for regulation of processes such as cell cycle distribution, apoptosis, and DNA damage repair. SHP-1 was highly expressed in NPC tissues in contrast to normal nasopharyngeal mucosa and was associated with local recurrence and metastasis after radiotherapy in NPC patients [25], which could point to its roles in chemoradiation resistance.

11. C-Jun Gene

C-Jun is a major constituent of activating protein transcription factor that transduces multiple mitogen growth signals [26]. Overexpression of c-Jun/AP-1 has been associated with tumor invasion, metastasis, and prognosis in many human cancers [26][27]. Previous studies have shown that the expression of cyclin is positively correlated with radiation resistance. The expression of c-Jun was significantly upregulated and may be associated with the radio-resistance of NPC [28]. C-Jun may play an essential role in radio-resistance through the EGFR pathway or AP-1. The finding implies that the overexpression of c-Jun may serve as a potential target to enhance the radiation sensitivity for NPC therapy.

12. MicroRNA (miRNA)

MicroRNAs are short non-coding RNAs, typically 21–23 nucleotides long, that function in post-transcriptional gene regulation typically through translation inhibition and mRNA degradation [29]. Specific individual miRNAs may be informative of changes with respect to cellular growth, proliferation, metastases, and apoptosis and for use in diagnostic or prognostic assessments. Other groups of miRNAs might guide the course of treatment by reflecting NPC resistance to radiotherapy or chemotherapy [30].
NPC has a high degree of expression of EBV-encoded microRNAs, particularly BART miRNAs, which are encoded from the viral genome’s BamHI-A region. According to growing data, ebv-mir-BARTs play a vital role in host cell survival, immunological evasion, cell proliferation, cell apoptosis, and cancer metabolism, boosting NPC formation. In NPC cell lines and primary tissues, ebv-mir-BART21 and ebv-mir-BART22 are substantially expressed [31]. Importantly, BART22 can suppress the host immune response by downregulating LMP2A at the translational level, allowing NPC cancer cells to survive.
The importance of miRNAs in chemotherapy response has been demonstrated in NPC. For instance, miR-3188 has been found to inhibit cell growth and resistance to fluorouracil by directly targeting the mechanistic target of rapamycin kinase gene, MTOR, and regulating the cell cycle. Another study reported that the metastasis suppressor miR-29c can also increase NPC cells’ sensitivity to both radiotherapy and cisplatin-based chemotherapy [32]. Tian et al. described the molecular mechanisms of miRNA involved in the radiotherapy resistance of nasopharyngeal carcinoma by affecting apoptosis, DNA damage repair, and cell cycle progression of nasopharyngeal carcinoma cells [33].

13. Cancer Stem Cells (CSCs)

Cancer stem cells (CSCs) are elucidated as cells that can perpetuate themselves via autorestoration. These cells are highly resistant to current therapeutic approaches and are the main reason for cancer recurrence. CSCs have been observed to drive tumor initiation and tumor chemoradioresistance [33][21][34][35]. Emerging evidence strongly supports that cancer stem cells may contribute to NPC’s resistance to chemoradiation [36][37]. CSCs have stronger radioresistance and particular molecular features that protect them from radiation-induced damage as compared to tumor cells’ mass [8]. This promotes the chemoradiation resistance in NPC patients.
Imperatively, CSCs’ subpopulations are able to express various markers that have different phenotypic and functional characteristics, even within the same tumor [38]. The propagation of CSCs to maintain the tumor initiation ability refers to the self-renewal of CSCs [39][40]. The CSCs’ resistance to chemoradiation is the source of local recurrence and metastasis [41]. CSCs are highly tumorigenic compared to the other cancer cells and are largely responsible for numerous biological characteristics of cancer [42][43]. CSCs have been found to have a strong DNA repair capacity in a variety of tumor types. Protection from oxidative stress by ROS scavenging, activation of anti-apoptotic pathways, and protection by microenvironmental niche 3 are among the mechanisms of CSC radioresistance.

References

  1. Peng, Y.; Li, X.; Liu, H.; Deng, X.; She, C.; Liu, C.; Wang, X.; Liu, A. microRNA-18a from M2 macrophages inhibits TGFBR3 to promote nasopharyngeal carcinoma progression and tumor growth via TGF-β signaling pathway. Nanoscale Res. Lett. 2020, 15, 196.
  2. Su, Z.; Li, G.; Liu, C.; Ren, S.; Tian, Y.; Liu, Y.; Qiu, Y. Ionizing radiation promotes advanced malignant traits in nasopharyngeal carcinoma via activation of epithelial-mesenchymal transition and the cancer stem cell phenotype. Oncol. Rep. 2016, 36, 72–78.
  3. Guan, S.; Wei, J.; Huang, L.; Wu, L. Chemotherapy and chemo-resistance in nasopharyngeal carcinoma. Eur. J. Med. Chem. 2020, 207, 112758.
  4. Tan, Z.; Xiao, L.; Tang, M.; Bai, F.; Li, J.; Li, L.; Shi, F.; Li, N.; Li, Y.; Du, Q.; et al. Targeting CPT1A-mediated fatty acid oxidation sensitizes nasopharyngeal carcinoma to radiation therapy. Theranostics 2018, 8, 2329–2347.
  5. Wu, S.L.; Li, Y.J.; Liao, K.; Shi, L.; Zhang, N.; Liu, S.; Hu, Y.Y.; Li, S.L.; Wang, Y. 2-Methoxyestradiol inhibits the proliferation and migration and reduces the radio-resistance of nasopharyngeal carcinoma CNE-2 stem cells via NF-κB/HIF-1 signalling pathway inactivation and EMT reversal. Oncol. Rep. 2017, 37, 793–802.
  6. Yang, Y.; Zhou, H.; Zhang, G.; Xue, X. Targeting the canonical Wnt/β-catenin pathway in cancer radioresistance. Updates on the molecular mechanisms. J. Can. Res. Ther. 2019, 15, 272–277.
  7. Cheng, C.; Geng, F.; Cheng, X.; Guo, D. Lipid metabolism reprogramming and its potential targets in cancer. Cancer Commun. 2018, 38, 27.
  8. Zhan, Y.; Fan, S. Multiple mechanisms involving in radioresistance of nasopharyngeal carcinoma. J. Cancer 2020, 11, 4193–4204.
  9. Zhong, Q.; Liu, Z.H.; Lin, Z.R.; Hu, Z.D.; Yuan, L.; Liu, Y.M.; Zhou, A.J.; Xu, L.H.; Hu, L.J.; Wang, Z.F.; et al. The RARS-MAD1L1 fusion gene induces cancer stem cell-like properties and therapeutic resistance in nasopharyngeal carcinoma. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2018, 24, 659–673.
  10. Yang, L.; Zhu, J.; Zhang, J.; Bao, B.-J.; Guan, C.-Q.; Yang, X.-J.; Liu, Y.-H.; Huang, Y.-J.; Ni, R.-Z.; Ji, L.-L. Far upstream element-binding protein 1 (FUBP1) is a potential c-Myc regulator in esophageal squamous cell carcinoma (ESCC) and its expression promotes ESCC progression. Tumor Biol. 2016, 37, 4115–4126.
  11. Sharbeen, G.; McCarroll, J.; Goldstein, D.; Phillips, P.A. Exploiting base excision repair to improve therapeutic approaches for pancreatic cancer. Front. Nutr. 2012, 2, 10.
  12. Wang, J.; Guo, C.; Gong, X.; Ao, F.; Huang, Y.; Huang, L.; Tang, Y.; Jiang, C.; Xie, X.; Dong, Q.; et al. The impacts of genetic polymorphisms in genes of base excision repair pathway on the efficacy and acute toxicities of (chemo)radiotherapy in patients with nasopharyngeal carcinoma. Oncotarget 2017, 8, 78633–78641.
  13. Kuang, C.M.; Fu, X.; Hua, Y.J.; Shuai, W.D.; Ye, Z.H.; Li, Y.; Peng, Q.H.; Li, Y.Z.; Chen, S.; Qian, C.N.; et al. BST2 confers cisplatin resistance via NF-κB signalling in nasopharyngeal cancer. Cell Death Dis. 2017, 8, e2874.
  14. Li, Y.Y.; Chung, G.T.; Lui, V.W.; To, K.F.; Ma, B.B.; Chow, C.; Woo, J.K.; Yip, K.Y.; Seo, J.; Hui, E.P.; et al. Exome and genome sequencing of nasopharynx cancer identifies NF-κB pathway activating mutations. Nat. Commun. 2017, 8, 14121.
  15. Verhoeven, R.J.; Tong, S.; Zhang, G.; Zong, J.; Chen, Y.; Jin, D.Y.; Chen, M.R.; Pan, J.; Chen, H. NF-κB signaling regulates expression of Epstein-Barr virus BART MicroRNAs and long noncoding RNAs in nasopharyngeal carcinoma. J. Virol. 2016, 90, 6475–6488.
  16. Rinkenbaugh, A.L.; Baldwin, A.S. The NF-κB pathway and cancer stem cells. Cells 2016, 5, 16.
  17. Guo, X.B.; Ma, W.L.; Liu, L.J.; Huang, Y.L.; Wang, J.; Huang, L.H.; Peng, X.D.; Yin, J.Y.; Li, J.G.; Chen, S.J.; et al. Effects of gene polymorphisms in the endoplasmic reticulum stress pathway on clinical outcomes of chemoradiotherapy in Chinese patients with nasopharyngeal carcinoma. Acta Pharmacol. Sin. 2017, 38, 571–580.
  18. Zhao, Y.; Yi, J.; Tao, L.; Huang, G.; Chu, X.; Song, H.; Chen, L. Wnt signaling induces radioresistance through upregulating HMGB1 in esophageal squamous cell carcinoma. Cell Death Dis. 2018, 9, 433.
  19. Zhang, R.; Li, S.W.; Liu, L.; Yang, J.; Huang, G.; Sang, Y. TRIM11 facilitates chemoresistance in nasopharyngeal carcinoma by activating the β-catenin/ABCC9 axis via p62-selective autophagic degradation of Daple. Oncogenesis 2020, 9, 45.
  20. Yu, J.; Huang, Y.; Liu, L.; Wang, J.; Yin, J.; Huang, L.; Chen, S.; Li, J.; Yuan, H.; Yang, G.; et al. Genetic polymorphisms of Wnt/β-catenin pathway genes are associated with the efficacy and toxicities of radiotherapy in patients with nasopharyngeal carcinoma. Oncotarget 2016, 7, 82528–82537.
  21. Chi, H.C.; Tsai, C.Y.; Tsai, M.M.; Yeh, C.T.; Lin, K.H. Roles of long noncoding RNAs in recurrence and metastasis of radiotherapy-resistant cancer stem cells. Int. J. Mol. Sci. 2017, 18, 1903.
  22. Jiang, C.; Li, X.; Zhao, H.; Liu, H. Long non-coding RNAs: Potential new biomarkers for predicting tumor invasion and metastasis. Mol. Cancer 2016, 15, 62.
  23. Li, G.; Liu, Y.; Liu, C.; Su, Z.; Ren, S.; Wang, Y.; Deng, T.; Huang, D.; Tian, Y.; Qiu, Y. Genome-wide analyses of long noncoding RNA expression profiles correlated with radioresistance in nasopharyngeal carcinoma via next-generation deep sequencing. BMC Cancer 2016, 16, 719.
  24. Chen, Q.N.; Wei, C.C.; Wang, Z.X.; Sun, M. Long non-coding RNAs in anti-cancer drug resistance. Oncotarget 2017, 8, 1925–1936.
  25. Pan, X.; Meng, R.; Yu, Z.; Mou, J.; Liu, S.; Sun, Z.; Peng, G. Quinalizarin enhances radiosensitivity of nasopharyngeal carcinoma cells partially by suppressing SHP-1 expression. Int. J. Oncol. 2016, 48, 1073–1084.
  26. Gao, L.; Huang, S.; Ren, W.; Zhao, L.; Li, J.; Zhi, K.; Zhang, Y.; Qi, H.; Huang, C. Jun activation domain-binding protein 1 expression in oral squamous cell carcinomas inversely correlates with the cell cycle inhibitor p27. Med. Oncol. 2012, 29, 2499–2504.
  27. Gonzalez-Villasana, V.; Gutiérrez-Puente, Y.; Tari, A.M. Cyclooxygenase-2 utilizes Jun N-terminal kinases to induce invasion, but not tamoxifen resistance, in MCF-7 breast cancer cells. Oncol. Rep. 2013, 30, 1506–1510.
  28. Guo, S.; Zhu, X.; Ge, L.; Qu, S.; Li, L.; Su, F.; Guo, Y. RNAi-mediated knockdown of the c-jun gene sensitizes radioresistant human nasopharyngeal carcinoma cell line CNE-2R to radiation. Oncol. Rep. 2015, 33, 1155–1160.
  29. Jennifer, Y.Y.K.; Pamela, P.; Jeff, P.B.; Kenneth, W.Y.; Fei-Fei, L. The complexity of mi-croRNAs in human cancer. J. Radiat. Res. 2016, 57, i106–i111.
  30. Spence, T.; Bruce, J.; Yip, K.; Liu, F. MicroRNAs in nasopharyngeal carcinoma. Chin. Clin. Oncol. 2016, 5, 17.
  31. Wang, Y.; Guo, Z.; Shu, Y.; Zhou, H.; Wang, H.; Zhang, W. BART miRNAs: An unimaginable force in the development of nasopharyngeal carcinoma. Eur. J. Cancer Prev. 2017, 26, 144–150.
  32. Tian, Y.; Tang, L.; Yi, P.; Pan, Q.; Han, Y.; Shi, Y.; Rao, S.; Tan, S.; Xia, L.; Lin, J.; et al. MiRNAs in radiotherapy resistance of nasopharyngeal carcinoma. J. Cancer 2020, 11, 3976–3985.
  33. Chen, W.; Hu, G.H. Biomarkers for enhancing the radiosensitivity of nasopharyngeal carcinoma. Cancer Biol. Med. 2015, 12, 23–32.
  34. Yu, S.S.; Cirillo, N. The molecular markers of cancer stem cells in head and neck tumors. J. Cell. Physiol. 2020, 235, 65–73.
  35. Atashzar, M.R.; Baharlou, R.; Karami, J.; Abdollahi, H.; Rezaei, R.; Pourramezan, F.; Moghaddam, S.H.Z. Cancer stem cells: A review from origin to therapeutic implications. J. Cell Physiol. 2020, 235, 790–803.
  36. Lu, Y.; Liang, Y.; Zheng, X.; Deng, X.; Huang, W.; Zhang, G. EVI1 promotes epithelial-to-mesenchymal transition, cancer stem cell features and chemo-/radioresistance in nasopharyngeal carcinoma. J. Exp. Clin. Cancer Res. 2019, 38, 82.
  37. Zhang, G.; Zhang, S.; Ren, J.; Yao, C.; Zhao, Z.; Qi, X.; Zhang, X.; Wang, S.; Li, L. Salinomycin may inhibit the cancer stem-like populations with increased chemoradioresistance that nasopharyngeal cancer tumorspheres contain. Oncol. Lett. 2018, 16, 2495–2500.
  38. Yoganandarajah, V.; Patel, J.; van Schaijik, B.; Bockett, N.; Brasch, H.D.; Paterson, E.; Sim, D.; Davis, P.F.; Roth, I.M.; Itinteang, T.; et al. Identification of cancer stem cell subpopulations in head and neck metastatic malignant melanoma. Cells 2020, 9, 324.
  39. Lee, C.H.; Yu, C.C.; Wang, B.Y.; Chang, W.W. Tumorsphere as an effective in vitro platform for screening anti-cancer stem cell drugs. Oncotarget 2016, 7, 1215–1226.
  40. Yu, H.H.; Featherston, T.; Tan, S.T.; Chibnall, A.M.; Brasch, H.D.; Davis, P.F.; Itinteang, T. Characterization of cancer stem cells in moderately differentiated buccal mucosal squamous cell carcinoma. Front. Surg. 2016, 3, 46.
  41. Koh, S.P.; Brasch, H.D.; de Jongh, J.; Itinteang, T.; Tan, S.T. Cancer stem cell subpopulations in moderately differentiated head and neck cutaneous squamous cell carcinoma. Heliyon 2019, 5, e02257.
  42. Baillie, R.; Tan, S.T.; Itinteang, T. Cancer stem cells in oral cavity squamous cell carcinoma: A review. Front. Oncol. 2017, 7, 112.
  43. Chen, K.H.; Guo, Y.; Li, L.; Qu, S.; Zhao, W.; Lu, Q.T.; Zhu, X.D. Cancer stem cell-like characteristics and telomerase activity of the nasopharyngeal carcinoma radioresistant cell line CNE-2R. Cancer Med. 2018, 7, 4755–4764.
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Norhafiza Mat Lazim
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