Current landscape of targeted therapy in esophageal squamous cell carcinoma

Abstract

Esophageal cancer is the seventh most common malignancy worldwide and is primarily categorized into adenocarcinoma and squamous cell carcinoma (SCC), with the predominant histological type varying by region. In Western countries, including the United States, adenocarcinoma is more prevalent, whereas in East Asian countries, SCC is more common, with it constituting 86% of cases in Japan. Although there has been an increasing trend of adenocarcinoma in Western populations, SCC still accounts for the majority of esophageal cancer cases globally. Cytotoxic chemotherapy has been the mainstay of treatment, however, targeted therapies including EGFR, FGFR, PI3K, or CDK4/6, despite showing preliminary efficacy signals, have not yet received regulatory approval. Recently, immune checkpoint inhibitors (ICIs) have shown therapeutic efficacy and have been approved as a monotherapy or combination therapy for advanced esophageal SCC (ESCC). Although PD-L1 expression is the only clinically applicable biomarker for first-line therapy with ICIs in ESCC, responses to ICIs are various, and novel predictive biomarkers are under investigation. Furthermore, novel antibody-drug conjugates (ADC) hold promise for advanced ESCC. This review includes the current landscape and future perspectives of potential targeted therapy for advanced ESCC.

Keywords: Biomarker; Esophageal cancer; Esophageal squamous cell carcinoma; Immune checkpoint inhibitor; Immunotherapy; Precision oncology; Targeted therapy.