Abstract
Pharmaceutical therapies are essential for esophageal cancer (EC). For the advanced EC, the neoadjuvant therapy regimen, including chemotherapy plus radiotherapy and/or immunotherapy, is effective to achieve clinical benefit, even pathological complete response. For the unresectable, recurrent, and metastatic EC, the pharmaceutical therapy is the limited effective regimen to alleviate the disease and prolong the progression-free survival and overall survival. In this review, we focus on the pharmaceutical applications in EC treatment including cytotoxic agents, molecular targeted antibodies, and immune checkpoint inhibitors (ICIs). The chemotherapy regimen is based on cytotoxic agents such as platinum-based complexes, fluorinated pyrimidines and taxenes. Although the cytotoxic agents have been developed in past decades, the standard chemotherapy regimen is still the cisplatin and 5-FU or paclitaxel because the derived drugs have no significant advantages of overcoming the shortcomings of side effects and drug resistance. The targeted molecular therapy is an essential supplement for chemotherapy; however, there are only a few targeted therapies available in clinical practice. Trastuzumab and ramucirumab are the only two molecular therapy drugs which are approved by the US Food and Drug Administration to treat advanced and/or metastatic EC. Although the targeted therapy usually achieves effective benefits in the early stage therapy of EC, the patients will always develop drug resistance during treatment. ICIs have had a significant impact on routine clinical practice in cancer treatment. The anti-programmed cell death-1 monoclonal antibodies pembrolizumab and nivolumab, as the ICIs, are recommended for advanced EC by several clinical trials. However, the significant issues of pharmaceutical treatment are still the dose-limiting side effects and primary or secondary drug resistance. These defects of pharmaceutical therapy restrain the clinical application and diminish the effectiveness of treatment.
Highlights
Esophageal cancer (EC) is a global health challenge
The apoptosis would be activated while the DNA repair fails or excessive DNA lesions occurs after platinum agents and mitochondria will generate surplus reactive oxygen species (ROS) to kill the cells
The molecular characterization of esophageal adenocarcinoma (EAC) is divided into four etiological/genetic subtypes based on gastric adenocarcinoma molecular characterization classification (Cancer Genome Atlas Research Network, 2014): (1) EBV-associated tumors; (2) Microsatellite instability (MSI) tumors commonly with PIK3CA, EGFR and human epidermal growth factor receptor 2 (HER2) mutations; (3) Genomically stable tumors, (4) Chromosomally instability (CIN) tumors with TP53 mutations as well as receptor tyrosine kinases (RTK)/RAS, VEGFR, and p110 amplifications (Barsouk et al, 2019)
Summary
Chengyi Mao1†, Xiaoxi Zeng2†, Chao Zhang, Yushang Yang, Xin Xiao, Siyuan Luan, Yonggang Zhang3,4,5* and Yong Yuan1*. For the advanced EC, the neoadjuvant therapy regimen, including chemotherapy plus radiotherapy and/or immunotherapy, is effective to achieve clinical benefit, even pathological complete response. We focus on the pharmaceutical applications in EC treatment including cytotoxic agents, molecular targeted antibodies, and immune checkpoint inhibitors (ICIs). The cytotoxic agents have been developed in past decades, the standard chemotherapy regimen is still the cisplatin and 5-FU or paclitaxel because the derived drugs have no significant advantages of overcoming the shortcomings of side effects and drug resistance. The significant issues of pharmaceutical treatment are still the dose-limiting side effects and primary or secondary drug resistance. These defects of pharmaceutical therapy restrain the clinical application and diminish the effectiveness of treatment
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