Although surgical techniques and adjuvant therapies have un­ dergone progressive developments in past decades, the thera­ peuticoutcomes for esophageal  squamouscellcarcinoma  (ES­ CC) remain poor. ldentification of new biomarkers for ESCC has signi 如 an tly improved understanding of the molecular pathogen­ esis of ESCC, allowing for more personalized treatments for af­ fected patients. Despite the significant advances in molecular testing and discoveries of new and promising therapeutics, effi­ cient treatments for advanced and metastaticESCC remain in­ sufficient. This review summarizes thecurrent understanding of the molecular pathways and their  relevance  to  the development of novel therapeutics, specifically focusing on the phosphoinosit­ ide 3-kinase / AKT / mammalian target of rapamycin, Wnt/[3 - Catenin, MARK/ERK, Hippo pathway, the p53-dependent path­ way, and other pathways. In addition, the molecular pathways driving ESCC and the recent advances in targeted therapies are also discussed, which could provide insights on identifying po­ tential targets with anti-tumor activity for the treatment of ad­vanced ESCC.

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