Genetic and Epigenetic Biomarkers for Diagnosis and Prognosis of Head and Neck Cancer

Head and neck cancers (HNCs) represent a heterogeneous group of malignancies originating from the mucosal linings of the oral cavity, pharynx, and larynx. Early detection and accurate prognosis are pivotal in improving survival rates and patient outcomes. Recent advancements in molecular biology have underscored the importance of genetic and epigenetic biomarkers in HNCs, paving the way for personalized medicine. This article delves into the detailed molecular mechanisms and clinical implications of these biomarkers Genetic biomarkers are specific DNA sequences whose alterations are linked to cancer development and progression. These alterations include mutations, amplifications, deletions, and translocations. TP۵۳ mutations are among the most significant in HNCs. TP۵۳ encodes the p۵۳ protein, a crucial tumor suppressor that regulates the cell cycle and promotes apoptosis in response to DNA damage. Mutations in TP۵۳, which occur in over ۵۰% of HNC cases, often result in a dysfunctional p۵۳ protein that cannot bind DNA effectively, leading to impaired cell cycle arrest and evasion of apoptosis. The presence of TP۵۳ mutations is associated with poor prognosis, resistance to therapy, and increased tumor aggressiveness. Detection of TP۵۳ mutations can assist in identifying high-risk patients and tailoring more aggressive treatment strategies. Another critical genetic biomarker is EGFR, the gene encoding the epidermal growth factor receptor, a tyrosine kinase involved in regulating cell growth and survival through the activation of downstream signaling pathways such as RAS-RAF-MEK-ERK and PI۳K-AKT. Overexpression or mutations in EGFR lead to constitutive activation of these pathways, promoting uncontrolled cell proliferation and survival. EGFR alterations are found in a significant subset of HNCs and are linked to poor clinical outcomes. Targeting EGFR with monoclonal antibodies (e.g., cetuximab) or tyrosine kinase inhibitors can inhibit tumor growth and improve patient survival.PIK۳CA mutations also play a significant role in HNCs. PIK۳CA encodes the p۱۱۰α catalytic subunit of the PI۳K enzyme, which is involved in the PI۳K-AKT signaling pathway that regulates cell growth, proliferation, and survival. Mutations in PIK۳CA result in constitutive activation of this pathway, driving oncogenesis. PIK۳CA mutations are present in a subset of HNCs and are associated with tumorigenesis and resistance to conventional therapies. Inhibitors targeting the PI۳K-AKT-mTOR pathway are being explored as potential therapeutic options.

کلیدواژه ها:

head and neck cancer ، prognosis ، personalized medicine ، Genetic biomarkers