Unraveling the Molecular Pathogenesis of Parotid Gland Tumours: Insights and Implications

Sierra Crescencia^*
*Correspondence: Sierra Crescencia, Department of Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania, Email:

Introduction

Parotid gland tumours are among the most diverse neoplasms of the head and neck region. While they are relatively rare, they present a significant challenge in diagnosis and treatment due to their heterogeneous nature. The molecular pathogenesis of these tumours has garnered significant interest, providing insights into their development and potential therapeutic implications. This article explores the molecular mechanisms underlying parotid gland tumours, their clinical implications and potential therapeutic strategies. Deregulation of the PI3K/AKT/mTOR pathway is a common feature in various cancers, including parotid gland tumours. Mutations in genes encoding components of this pathway, such as PIK3CA and PTEN, can lead to aberrant activation, promoting tumour growth and survival. The tumour microenvironment, comprising stromal cells, immune cells and extracellular matrix components, plays a critical role in tumour progression.

Description

Overview of parotid gland tumours

Parotid gland tumours can be broadly classified into benign and malignant categories. Benign tumours, such as pleomorphic adenomas and Warthin’s tumours, are more common, whereas malignant tumours include mucoepidermoid carcinoma, adenoid cystic carcinoma and acinic cell carcinoma. Each of these tumours exhibits distinct histological and molecular characteristics, necessitating tailored diagnostic and treatment approaches [1].

Molecular pathogenesis

Specific gene mutations have been implicated in the development of parotid gland tumours. For instance, the translocation t (11;19)(q21;p13) resulting in the CRTC1-MAML2 fusion gene is commonly associated with mucoepidermoid carcinoma. This fusion gene acts as an oncogenic driver by altering normal cellular signalling pathways. Chromosomal abnormalities, such as translocations and deletions, play a crucial role in tumour genesis. For example, translocation t(6;9)(q22-23;p23-24) resulting in the MYB-NFIB fusion gene is frequently observed in adenoid cystic carcinoma, leading to the Deregulation of MYB, a transcription factor involved in cell growth and differentiation [2]. Epigenetic changes, including DNA methylation and histone modifications, contribute to the pathogenesis of parotid gland tumours. Hypo methylation of tumour suppressor genes and hypo methylation of oncogenes can disrupt normal cellular function, promoting tumour development. For instance, Hypo methylation of the p16INK4a gene, a crucial regulator of the cell cycle, has been observed in various salivary gland tumours.

Aberrations in RTKs and their downstream signalling pathways are frequently observed in parotid gland tumours. Overexpression or mutations in RTKs, such as EGFR and HER2, can lead to uncontrolled cell proliferation and survival. Targeting these pathways with specific inhibitors has shown promise in preclinical studies. Deregulation of the PI3K/AKT/mTOR pathway is a common feature in various cancers, including parotid gland tumours. Mutations in genes encoding components of this pathway, such as PIK3CA and PTEN, can lead to aberrant activation, promoting tumour growth and survival. The tumour microenvironment, comprising stromal cells, immune cells and extracellular matrix components, plays a critical role in tumour progression. Interactions between tumour cells and the microenvironment can influence tumour behaviour and response to therapy. For example, the presence of tumour-associated macrophages has been associated with a poor prognosis in some parotid gland tumours [3].

Clinical implications

The molecular characterization of parotid gland tumours has significantly improved diagnostic accuracy. Techniques such as Fluorescence In Situ Hybridization (FISH) and Next-Generation Sequencing (NGS) allow for the detection of specific genetic alterations, aiding in the differentiation between benign and malignant tumours. Identifying these molecular markers can also provide prognostic information, guiding treatment decisions. Understanding the molecular pathways involved in parotid gland tumours has paved the way for targeted therapies. Inhibitors of RTKs, such as cetuximab and trastuzumab, have shown efficacy in preclinical models. Additionally, PI3K/AKT/mTOR inhibitors, like everolimus, are being investigated for their potential to inhibit tumour growth. The role of the immune system in parotid gland tumours is an emerging area of research. Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, have shown promise in other head and neck cancers and are being explored in clinical trials for parotid gland tumours [4]. Molecular markers can also provide prognostic information, helping to predict disease progression and patient outcomes. For instance, the presence of the CRTC1-MAML2 fusion gene in mucoepidermoid carcinoma is associated with a better prognosis, while MYB-NFIB fusion in adenoid cystic carcinoma is linked to a more aggressive clinical course [5].

Future directions

The study of the molecular pathogenesis of parotid gland tumours is still evolving. Future research should focus on the identification of novel genetic and epigenetic alterations, the development of more effective targeted therapies and the exploration of the tumour microenvironment. Additionally, large-scale clinical trials are needed to validate the efficacy of emerging therapeutic strategies. Understanding the molecular pathways involved in parotid gland tumours has paved the way for targeted therapies. Inhibitors of RTKs, such as cetuximab and trastuzumab, have shown efficacy in preclinical models. Additionally, PI3K/AKT/mTOR inhibitors, like everolimus, are being investigated for their potential to inhibit tumour growth. The role of the immune system in parotid gland tumours is an emerging area of research. Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, have shown promise in other head and neck cancers and are being explored in clinical trials for parotid gland tumours.

Conclusion

The molecular pathogenesis of parotid gland tumours involves a complex interplay of genetic, epigenetic and micro environmental factors. Advances in molecular diagnostics and targeted therapies hold promise for improving the diagnosis, treatment and prognosis of these tumours. Continued research in this field is essential to unravel the complexities of parotid gland tumour biology and to develop more effective therapeutic strategies.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Yapijakis, Christos, Stefania Kalogera, Veronica Papakosta and Stavros Vassiliou, et al. "The hamster model of sequential oral carcinogenesis: an update." In vivo 33 (2019): 1751-1755.

   Google Scholar, Crossref, Indexed at

2. Roehling, Stefan, Monika Astasov‐Frauenhoffer, Irmgard Hauser‐Gerspach and Olivier Braissant, et al. "In vitro biofilm formation on titanium and zirconia implant surfaces." J Periodontol 88 (2017): 298-307.

   Google Scholar, Crossref, Indexed at

3. Tsujimoto, Yoshihide, Lawrence R. Finger, Jorge Yunis and Peter C. Nowell, et al. "Cloning of the chromosome breakpoint of neoplastic B cells with the t (14; 18) chromosome translocation." Sci 226 (1984): 1097-1099.

   Google Scholar, Crossref, Indexed at

4. Souza, João Gabriel Silva, Martinna Mendonca Bertolini, Raphael Cavalcante Costa and Bruna Egumi Nagay, et al. "Targeting implant-associated infections: Titanium surface loaded with antimicrobial." Sci 24 (2021).

   Google Scholar, Crossref, Indexed at

5. Li, Mei, Zheng Ma, Ye Zhu and Hong Xia, et al. "Toward a molecular understanding of the antibacterial mechanism of copper‐bearing titanium alloys against Staphylococcus aureus." Adv Healthc Mater 5 (2016): 557-566.

   Google Scholar, Crossref, Indexed at