Targeted therapy for head and neck cancer: signaling pathways and clinical studies

Abstract

Head and neck cancer (HNC) is malignant, genetically complex and difficult to treat and is the sixth most frequent cancer, with tobacco, alcohol and human papillomavirus being major risk factors. Based on epigenetic data, HNC is remarkably heterogeneous, and treatment remains challenging. There is a lack of significant improvement in survival and quality of life in patients with HNC. Over half of HNC patients experience locoregional recurrence or distal metastasis despite the current multiple traditional therapeutic strategies and immunotherapy. In addition, resistance to chemotherapy, radiotherapy and some targeted therapies is common. Therefore, it is urgent to explore more effective and tolerable targeted therapies to improve the clinical outcomes of HNC patients. Recent targeted therapy studies have focused on identifying promising biomarkers and developing more effective targeted therapies. A well understanding of the pathogenesis of HNC contributes to learning more about its inner association, which provides novel insight into the development of small molecule inhibitors. In this review, we summarized the vital signaling pathways and discussed the current potential therapeutic targets against critical molecules in HNC, as well as presenting preclinical animal models and ongoing or completed clinical studies about targeted therapy, which may contribute to a more favorable prognosis of HNC. Targeted therapy in combination with other therapies and its limitations were also discussed.

Natural killer cell‐based signature: Prognostic analysis in head and neck squamous cell carcinoma

“…Over the past few decades, the advent of molecular‐targeted therapy has yielded significant clinical advancements in the management of HNSC. Regrettably, a majority of patients inevitably develop resistance to these targeted interventions, thereby perpetuating a bleak prognosis 2–5 . The utilization of immune checkpoint inhibitors (ICIs) has emerged as a novel therapeutic approach in the management of HNSCs 6–9 .…”

“…Regrettably, a majority of patients inevitably develop resistance to these targeted interventions, thereby perpetuating a bleak prognosis. [2][3][4][5] The utilization of immune checkpoint inhibitors (ICIs) has emerged as a novel therapeutic approach in the management of HNSCs. [6][7][8][9] Regrettably, the overall response rates and efficacy remain suboptimal, primarily because of the inherent "cold" nature of HNSCs characterized by an immunosuppressive tumor microenvironment (TME).…”

Dietary intake effects on severity of cancer treatment‐induced mucositis: A cross‐sectional study

“…Head and neck cancer is the sixth most common cancer globally and has become a global health concern 1 . Various treatment modalities are recommended for cancer patients, such as surgery, radiation therapy, chemotherapy, or a combination thereof, and long‐term follow‐up 2 .…”

“…Head and neck cancer is the sixth most common cancer globally and has become a global health concern. 1 Various treatment modalities are recommended for cancer patients, such as surgery, radiation therapy, chemotherapy, or a combination thereof, and long-term follow-up. 2 Chemotherapy and radiation therapy are nonsurgical methods used today to treat head and neck cancers, prolong survival rates, or completely cure the mass.…”

Rationale for Cotargeting Hepatocyte Growth Factor and Epidermal Growth Factor Receptor in Recurrent/Metastatic Head and Neck Cancer

“…11,12 Moreover, several studies have reported an inverse correlation between high EGFR copy number or overexpression and HPV status. 13 Preclinical studies reported that loss of EGFR 14,15 or TGFa 16 expression using genetic means (eg, antisense strategy or silent RNA knockdown) or therapeutic inhibition of EGFR 17,18 decreased the proliferation of HNSCC cells in vitro and in patient-derived xenografts in mouse models. 19 However, the effects were often modest as monotherapy but were enhanced when combined with another treatment such as chemotherapy 15 or radiotherapy, as shown for example in combination with cetuximab.…”