Mutational Landscape of Oral Squamous Cell Carcinoma Investigated Through the Developmental Dynamics of Oral Squamous Epithelium

Author:

Shafi Ovais1ORCID,Aakash 2,Haseeb Madiha1,Shah Syeda Urooba1,Madhwani Manwar1,Raveena 1,Kataria Disha Kumari1,Yaqub Muhammad Danial3

Affiliation:

1. Sindh Medical College - Jinnah Sindh Medical University / Dow University of Health Sciences, Karachi, Pakistan

2. Florida State University Cape Coral Hospital, USA

3. Lincoln County Hospital, Lincoln, UK

Abstract

Abstract

Background: Oral Squamous Cell Carcinoma (OSCC) poses a global health challenge, demanding an in-depth understanding of its mutational landscape. The complex mutational profile underscores the need for targeted therapies. OSCC's impact on crucial functions necessitates precise interventions for improved patient outcomes. This investigation into OSCC's mutational landscape through developmental biology aims to fill critical knowledge gaps, contributing possibly towards future personalized therapies and advancing our approach to this challenging malignancy. Methods: Databases, including PubMed, MEDLINE, Google Scholar, and open access/subscription-based journals were searched for published articles without any date restrictions, to investigate the mutational landscape of OSCC through the lens of developmental dynamics. Based on the criteria mentioned in the methods section, studies were systematically reviewed to investigate OSCC oncogenesis. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Results: This study into Oral Squamous Cell Carcinoma (OSCC) reveals a complex genetic landscape marked by mutations in key regulators including TP53, CASP8, CDKN2A, FAT1, PIK3CA, and RYR2. TP53 emerges as a central player, with mutations disrupting its tumor-suppressive functions and influencing developmental processes in OSCC. Dysregulated Notch1 signaling contributes to aberrant cell differentiation and tissue morphogenesis. JAK/STAT and SHH signaling, essential for normal oral epithelial development, exhibit dual dynamics in OSCC, influencing both normal developmental processes and tumorigenesis. Implications for precision medicine arise from the identified genetic alterations, offering potential targets for future therapeutic interventions. Notch1 and TP53 signaling pathways emerge as promising targets, while modulating JAK/STAT and SHH signaling presents challenges and opportunities for new therapeutic strategies. Conclusion: This study reveals genetic complexities and regulatory networks disrupted in OSCC carcinogenesis and also playing key roles in developmental dynamics of oral squamous epithelium. Key genes like TP53 and Notch1, integral to oral epithelial development, undergo dysregulation, influencing OSCC initiation. JAK/STAT and SHH signaling, crucial in normal development, exhibit dual roles, contributing to OSCC progression. This study also points to targeted therapeutic strategies that may emerge in future by investigating OSCC through developmental dynamics. Further research may provide deeper insights into the complex developmental biology, paving the way for enhanced interventions in OSCC.

Publisher

Research Square Platform LLC

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