Advances and challenges in the treatment of esophageal cancer

Abstract

Esophageal cancer (EC) is one of the most common cancers with high morbidity and mortality rates. EC includes two histological subtypes, namely esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). ESCC primarily occurs in East Asia, whereas EAC occurs in Western countries. The currently available treatment strategies for EC include surgery, chemotherapy, radiation therapy, molecular targeted therapy, and combinations thereof. However, the prognosis remains poor, and the overall five-year survival rate is very low. Therefore, achieving the goal of effective treatment remains challenging. In this review, we discuss the latest developments in chemotherapy and molecular targeted therapy for EC, and comprehensively analyze the application prospects and existing problems of immunotherapy. Collectively, this review aims to provide a better understanding of the currently available drugs through in-depth analysis, promote the development of new therapeutic agents, and eventually improve the treatment outcomes of patients with EC.

Keywords: Drug combination; Esophageal adenocarcinoma; Esophageal squamous cell carcinoma; Immune therapy; Molecular targeted therapy.

Graphical abstract

Figure 1

Schematic diagram of molecular targeted therapy for esophageal cancer. Frequent genetic alterations in key signaling pathways in esophageal cancer, involving insulin-like growth factor 1 receptor (IGF1R), receptor tyrosine-protein kinase ERBB-2 (HER2), epidermal growth factor receptor (EGFR), and tyrosine-protein kinase receptor UFO (AXL). Drugs, such as linsitinib, cetuximab, and R428, or other agents can specifically inhibit the components of the IGF1R-, EGFR-, and AXL-associated pathways. Regulation of these signaling pathways affects the proliferation, survival, migration, invasion, and differentiation of tumor cells, thereby inhibiting tumor growth.

Figure 2

Schematic diagram of immunotherapy for esophageal cancer. Dendritic cells (DCs), macrophages, natural killer (NK) cells, T cells, and B cells are all involved in immunotherapy against esophageal cancer. DCs are antigen-presenting cells that upon activation by exogenous or endogenous factors, participate in the immune responses mediated by CD4⁺ T or CD8⁺ T cells. The SIRPa–CD47 interaction is very critical between macrophages and tumor cells. Drugs, such as antibodies, that specifically disrupt this interaction can suppress the growth of tumor cells. T cells or NK cells are modified to generate chimeric antigen receptor (CAR) T cells or engineered NK cells, respectively, that can specifically kill tumor cells. After recruitment or activation, immune cells can play multifunctional roles in inducing tumor-cell apoptosis and death, thereby inhibiting tumor growth.