Changing landscape of advanced esophageal squamous cell carcinoma: Breakthroughs in systemic therapies (Review)

The treatment of advanced esophageal squamous cell carcinoma (ESCC) presents numerous challenges. Whereas conventional therapies such as chemotherapy, radiotherapy and targeted treatments have achieved some success. However, the substantial heterogeneity of the disease poses challenges in achieving comprehensive therapeutic coverage through a single treatment approach, because molecular subtyping remains insufficiently defined. Consequently, the response rate to targeted therapies is limited. Moreover, the issue of resistance to immunotherapy is becoming increasingly prominent, and reliable predictive biomarkers are lacking. Additionally, the regulatory mechanisms of the tumor microenvironment in metastatic lesions require further investigation. In recent years, the advent of immunotherapy and novel drug development has brought new hope, particularly with the clinical application of antibody‑drug conjugates, bispecific antibodies, novel immune checkpoint inhibitors, new targeted therapies, and cell and vaccine therapies, which have markedly improved patient survival. The present review summarizes the current therapeutic landscape for advanced ESCC and discusses the potential of future treatment strategies. Despite improvements in survival rates with existing treatments, the integration of emerging therapies with precision medicine may become key to future ESCC management, through driving personalized treatment approaches and multidisciplinary collaboration, and ultimately improving patient quality of life and clinical outcomes.