Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most incident cancer worldwide. More than half of HNSCC patients experience locoregional or distant relapse to treatment despite aggressive multimodal therapeutic approaches that include surgical resection, radiation therapy, and adjuvant chemotherapy. Before the arrival of immunotherapy, systemic chemotherapy was previously employed as the standard first-line protocol with an association of cisplatin or carboplatin plus 5-fluorouracil plus cetuximab (anti-EFGR antibody). Unfortunately, acquisition of therapy resistance is common in patients with HNSCC and often results in local and distant failure. Despite our better understanding of HNSCC biology, no other molecular-targeted agent has been approved for HNSCC. In this review, we outline the mechanisms of resistance to the therapeutic strategies currently used in HNSCC, discuss combination treatment strategies to overcome them, and summarize the therapeutic regimens that are presently being evaluated in early- and late-phase clinical trials.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most incident cancer worldwide, responsible for more than 700,000 cases worldwide per year and around 350,000 deaths, making it a fatal disease [1].Squamous cell cancers of the oral cavity, the pharynx, and the larynx are linked to smoking and alcohol consumption, and squamous cell carcinomas of the oropharynx are mostResistance to Therapy in Head and Neck Cancers commonly associated with human papilloma virus (HPV) infection, especially for young or nonsmoker patients
Cetuximab is used in the clinical routine as a radiation sensitizer alone or in combination with chemotherapy for the treatment of patients with recurrent or metastatic disease
Pembrolizumab was approved as a first-line therapy in patients who present with metastatic disease, and treatment with either pembrolizumab or nivolumab is used in the setting of cisplatin-refractory recurrent or metastatic HNSCC
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most incident cancer worldwide, responsible for more than 700,000 cases worldwide per year and around 350,000 deaths, making it a fatal disease [1]. Resistance to Therapy in Head and Neck Cancers commonly associated with human papilloma virus (HPV) infection, especially for young or nonsmoker patients. The incidence of the latter is rising, mostly among men [2]. More than half of HNSCC patients experience locoregional or distant relapse despite aggressive multimodal therapeutic approaches that include surgical resection (often with neck dissection), radiation therapy (exclusive or postoperative), and adjuvant chemotherapy given as a radiosensitizer [4]. If a salvage surgery (with R0 resection) or reirradiation is deemed unfeasible, systemic treatment options (detailed in this review) are proposed. We outline the mechanisms of resistance to the therapeutic strategies currently used in HNSCC, discuss combination treatment strategies to overcome them, and summarize the therapeutic regimens that are presently being evaluated in early- and late-phase clinical trials
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