Modeling nasopharyngeal carcinoma in three dimensions

Abstract

Abstract. Nasopharyngeal carcinoma (NPC) is a type of cancer endemic in Asia, including Malaysia, Southern China, Hong Kong and Taiwan. Treatment resistance, particularly in recurring cases, remains a challenge. Thus, studies to develop novel therapeutic agents are important. Potential therapeutic compounds may be effectively examined using two-dimensional (2D) cell culture models, three-dimensional (3D) spheroid models or in vivo animal models. The majority of drug assessments for cancers, including for NPC, are currently performed with 2D cell culture models. This model offers economical and high-throughput screening advantages. However, 2D cell culture models cannot recapitulate the architecture and the microenvironment of a tumor. In vivo models may recapitulate certain architectural and microenvironmental conditions of a tumor, however, these are not feasible for the screening of large numbers of compounds. By contrast, 3D spheroid models may be able to recapitulate a physiological microenvironment not observed in 2D cell culture models, in addition to avoiding the impediments of in vivo animal models. Thus, the 3D spheroid model offers a more representative model for the study of NPC growth, invasion and drug response, which may be cost-effective without forgoing quality. Contents1. Introduction 2. 2D cell culture models 3. In vivo animal models 4. 3D spheroid models 5. 3D spheroid models for high-throughput drug screening 6. NPC 3D spheroids 7. Conclusion IntroductionNasopharyngeal carcinoma (NPC) is a type of cancer that affects the nasopharynx, commonly at the posterior and superior region in the fossa of Rosenmüller (1). It is a geographically distinct cancer, which is prevalent in south-east Asia, southern China and southern Africa (2). Viral, dietary, hereditary and lifestyle factors have been identified as risk factors for NPC (2). Current NPC treatment consists of radiotherapy, chemotherapy or chemo-radiotherapy; treatment resistance, particularly in advanced and recurrent cases of NPC, remains a challenge (2). NPC is staged according to the TNM system, whereby T describes the primary tumor invasion to the tissue or organs near the nasopharynx, N describes the spread to the lymph nodes and M indicates the metastasis of the tumor. NPC is usually detected at a late stage (III or IV) (2). Early-stage NPC has unspecific and ambiguous clinical symptoms such as neck lumps, bloodstained sputum, mild hearing loss and a unilateral headache which may be ignored by its sufferer or misdiagnosed by a doctor (3). Ultimately, this leads to a late disease presentation as well as detection. The pathogenesis of NPC involves genetic and epigenetic changes in the nasopharyngeal epithelium (4). Previous studies have improved current understanding of the potential molecular targets and signaling pathways involved in NPC pathogenesis, which has assisted the development of targeted therapies for the treatment of NPC, including cetuximab (Erbitux

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

“…124,171,273,281 Researchers can utilize different matrix to reconstruct tumor microenvironment, which guarantees drug sensitivity, the alterations of signaling pathways and gene expression in tumor cells. 277 Benefiting from its simulation of body condition, they ensure the reliability and validity of the experimental results of the targeted drug candidates. However, the study used lapatinib, a tyrosine kinase inhibitor against EGFR, on HONE-1 spheroids exhibited that the drug did not diffuse effectively to core cells of mass.…”

Synergistic anti-proliferative effects of combination of ABT-263 and MCL-1 selective inhibitor A-1210477 on cervical cancer cell lines

“…Sensitivity of the cervical cancer cell lines to combination of ABT-263 and A-1210477 were performed in the 2D cell culture model. The 2D model is high-throughput and economical but it lacks the microenvironment that tumours encounter in vivo [ 32 , 33 ]. Given that A-1210477 may demonstrate poor bioavailability in vivo, future studies in three-dimensional (3D) spheroid models, in vivo models and later in clinical trials should test combination of orally bioavailable ABT-263 with next generation MCL-1 inhibitors with improved bioavailability properties [ 34 ].…”

Combinations of Indole based alkaloids fromMitragyna speciosa(Kratom) and cisplatin inhibit cell proliferation and migration of Nasopharyngeal carcinoma cell lines

“…Thus far, there is only one study which reports sensitivity of cancer cell lines to Mitragynine (Goh et al, 2014). The broad aim of the study is to investigate the sensitivity of NPC cancer cell lines to combination of cisplatin and mitragyna alkaloids, in 2D monolayer culture and in 3-dimensional spheroids, which resemble a microenvironment closer to tumours in vivo (Sankar et al, 2017).…”