Targeted Molecular Therapies in the Treatment of Esophageal Adenocarcinoma, Are We There Yet?

Abstract

Esophageal adenocarcinoma is one of the leading causes of cancer-related deaths worldwide. The incidence of esophageal adenocarcinoma has increased at an alarming rate in the Western world and long-term survival remains poor. Current treatment approaches involve a combination of surgery, chemotherapy, and radiotherapy. Unfortunately, standard first-line approaches are met with high rates of recurrence and metastasis. More recent investigations into the distinct molecular composition of these tumors have uncovered key genetic and epigenetic alterations involved in tumorigenesis and progression. These discoveries have driven the development of targeted therapeutic agents in esophageal adenocarcinoma. While many agents have been studied, therapeutics targeting the human epidermal growth factor receptor (HER2) and vascular endothelial growth factor (VEGF) pathways have demonstrated improved survival. More recent advances in immunotherapies have also demonstrated survival advantages with monoclonal antibodies targeting the programmed death ligand 1 (PD-L1). In this review we highlight recent advances of targeted therapies, specifically agents targeting receptor tyrosine kinases, small molecule kinase inhibitors, and immune checkpoint inhibitors. While targeted therapeutics and immunotherapies have significantly improved survival, the benefits are limited to patients whose tumors express biomarkers such as PD-L1 and HER2. Survival remains poor for the remainder of patients with esophageal adenocarcinoma, underscoring the critical need for development of novel treatment strategies.

Cross-talk between the microbiome and chronic inflammation in esophageal cancer: potential driver of oncogenesis

“…Standard therapy is limited to surgical or endoscopic resection and chemotherapy. The potential effect of targeted therapy on the prognosis of EC is still unclear, and options are limited to targeting the human epidermal growth factor receptor 2 (HER2) [27,28], epidermal growth factor receptor (EGFR) [29], or phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) [30]. The addition of specific EGFR or HER2 monoclonal antibodies to concurrent chemoradiation therapy did not exhibit any significant clinical response [26,27].…”

Proximal esophageal adenocarcinoma: A rare case report

“…Fortunately, our patient achieved a complete cure without needing any surgical procedures after the medical treatment. This non-surgical route is supported by literature indicating that for certain stages of esophageal cancer, chemoradiotherapy can be as effective as surgery in terms of survival rates, with the added benefits of preserving esophageal function and reducing operative risks [ 12 ].…”

Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy

“…BGT226, an imidazoquinoline derivative, is an ATP-competitive dual PI3K/mTORC1/C2 inhibitor [184]. LY302341 presented promising antitumor activity in esophageal adenocarcinoma [185]. Clinical research on PWT33597 in advanced malignancies has been developed, but no results have been posted.…”