Current Trends and Future Prospects of Molecular Targeted Therapy in Head and Neck Squamous Cell Carcinoma

Abstract

In recent years, advances in drug therapy for head and neck squamous cell carcinoma (HNSCC) have progressed rapidly. In addition to cytotoxic anti-cancer agents such as platinum-based drug (cisplatin and carboplatin) and taxane-based drugs (docetaxel and paclitaxel), epidermal growth factor receptor-tyrosine kinase inhibitors (cetuximab) and immune checkpoint inhibitors such as anti-programmed cell death-1 (PD-1) antibodies (nivolumab and pembrolizumab) have come to be used. The importance of anti-cancer drug therapy is increasing year by year. Therefore, we summarize clinical trials of molecular targeted therapy and biomarkers in HNSCC from previous studies. Here we show the current trends and future prospects of molecular targeted therapy in HNSCC.

Keywords: cetuximab; head and neck squamous cell carcinoma; immune checkpoint inhibitor; molecular targeted therapy; multi-oncogene panel test; photoimmunotherapy.

Figure 1

Treatment algorithm of R/M HNSCC. FP: 5-FU + cisplatin, PCE: paclitaxel + carboplatin + cetuximab, Cmab: cetuximab, Pem: pembrolizumab, CPS: combined positive score, BSC: best supportive care. Citations and modifications of Jpn J Chemother (Gan To Kagaku Ryoho). 2020, 47, 1050–1054.

Figure 2

Mechanisms for PD-L1 expression and definition of combined positive score (CPS). Citations and modifications of Nat Rev Cancer. 2016, 16, 275–287. Innate expression of membranous PD-L1 by tumor cells is thought to be driven by dysregulated signaling pathways, or chromosomal alterations and amplifications. In contrast, adaptive focal expression of PD-L1 by tumor cells and macrophages occurs at the interface of tumor cell nests with immune infiltrates secreting pro-inflammatory factors such as interferon-γ. The ligation of PD-L1 with PD-1 molecules will down-modulate T cell function, essentially creating a negative feedback loop that dampens antitumor immunity [37].

Figure 3

Near infrared photoimmunotherapy (NIR-PIT). Cetuximab-bound IR700 selectively binds to the surface of EGFR-positive tumor cells. The photo-activation at 690 nm selectively kills EGFR-expressing cells, thus allowing for targeted photodynamic therapy and the induction of immunogenic cell death. This triggers a systemic immune response that contributes to the eradication of malignant cells [60].