Keywords

Head and Neck Squamous Cell Carcinoma, senescence, senescence-associated secretory phenotype, tumor progression

Abstract

Head and Neck Squamous Cell Carcinoma (HNSCC) comprises a heterogeneous group of malignancies originating from the mucosal epithelium of the oral cavity, pharynx, and larynx. Accounting for approximately 4.5% of global cancer incidence and mortality, HNSCC poses a persistent public health concern. Major risk factors include tobacco use, alcohol consumption, and infection with high-risk Human Papillomavirus (HPV) strains. Although conventional treatments such as surgery, chemotherapy, and radiotherapy have improved patient outcomes, therapeutic resistance and tumor recurrence remain significant challenges. A growing body of evidence implicates therapy-induced cellular senescence as a key mechanism in treatment resistance. Senescence is a stable state of cell cycle arrest in response to stress or damage, classically considered tumor-suppressive by halting the proliferation of compromised cells. However, senescent cells can acquire a senescence-associated secretory phenotype (SASP), Marked by the release of inflammatory cytokines, chemokines, growth factors, and proteolytic enzymes. While SASP initially reinforces growth arrest and immune clearance, chronic presence of senescent cells in the tumor microenvironment may instead promote tumor progression. SASP’s can enhance inflammation, extracellular matrix remodeling, angiogenesis, and even stimulate proliferation and epithelial-to-mesenchymal transition in adjacent cells. This study aims to investigate the role of senescence in HNSCC and its impact on neighboring tumor and normal cells. Senescence models induced in HNSCC cell lines using X-ray irradiation, mimicking DNA damage from clinical therapies. Co-culture experiments used to assess how senescent cells influence non-senescent cells through paracrine signaling. Particular focus placed on profiling SASP components and identifying key molecules that may drive senescence escape or tumor-promoting phenotypes. By clarifying the dual role of senescence in HNSCC, this research informed the development of strategies to eliminate senescent cells or modulate the SASP to improve treatment outcomes and prevent relapse.

Completion Date

2025

Semester

Summer

Committee Chair

Masternak, Michal

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Biomedical Sciences

Format

PDF

Identifier

DP0029508

Language

English

Document Type

Thesis

Campus Location

College of Medicine

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