Overcoming Resistance to Standard-of-Care Therapies for Head and Neck Squamous Cell Carcinomas

• Published in: Cells (Basel, Switzerland) Switzerland), 2024-06, Vol.13 (12), p.1018
• Main Authors: Gauss, Chester, Stone, Logan D, Ghafouri, Mehrnoosh, Quan, Daniel, Johnson, Jared, Fribley, Andrew M, Amm, Hope M
• Format: Article
• Language: English
• Subjects: Antimitotic agents; Antineoplastic agents; Cancer; Cancer therapies; Care and treatment; cetuximab; Chemotherapy; chemotherapy resistance; cisplatin; clinical trials; DNA methylation; DNA Repair; Drug Resistance, Neoplasm; Epigenesis, Genetic; Epigenetic inheritance; Epigenetics; Head and neck carcinoma; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - therapy; HNSCC; Humans; Immune checkpoint inhibitors; Mortality; Mutation; oral cancer; Radiation therapy; Radiotherapy; Review; Signal Transduction; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - pathology; Squamous Cell Carcinoma of Head and Neck - therapy; Standard of Care
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells13121018

Although there have been some advances during in recent decades, the treatment of head and neck squamous cell carcinoma (HNSCC) remains challenging. Resistance is a major issue for various treatments that are used, including both the conventional standards of care (radiotherapy and platinum-based chemotherapy) and the newer EGFR and checkpoint inhibitors. In fact, all the non-surgical treatments currently used for HNSCC are associated with intrinsic and/or acquired resistance. Herein, we explore the cellular mechanisms of resistance reported in HNSCC, including those related to epigenetic factors, DNA repair defects, and several signaling pathways. This article discusses these mechanisms and possible approaches that can be used to target different pathways to sensitize HNSCC to the existing treatments, obtain better responses to new agents, and ultimately improve the patient outcomes.