Potent molecular-targeted therapies for advanced esophageal squamous cell carcinoma

Abstract

Esophageal cancer (EC) remains a public health concern with a high mortality and disease burden worldwide. Esophageal squamous cell carcinoma (ESCC) is a predominant histological subtype of EC that has unique etiology, molecular profiles, and clinicopathological features. Although systemic chemotherapy, including cytotoxic agents and immune checkpoint inhibitors, is the main therapeutic option for recurrent or metastatic ESCC patients, the clinical benefits are limited with poor prognosis. Personalized molecular-targeted therapies have been hampered due to the lack of robust treatment efficacy in clinical trials. Therefore, there is an urgent need to develop effective therapeutic strategies. In this review, we summarize the molecular profiles of ESCC based on the findings of pivotal comprehensive molecular analyses, highlighting potent therapeutic targets for establishing future precision medicine for ESCC patients, with the most recent results of clinical trials.

Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma

“…Mutations of the NOTCH1 gene were more frequently observed in esophageal NECs compared to the other GEP-NECs [ 11 , 12 , 57 ], and the Notch signaling pathway is constitutively suppressed by the downregulation of Notch receptors and effectors, as well as the overexpression of Notch antagonists, such as DLL3 [ 57 , 58 ]. In addition, esophageal NECs exhibit a lower frequency of somatic copy number variants that are frequently altered in conventional esophageal cancers, such as CDKN2A and CCND1 in the cell cycle pathway and ERBB2 in the RTK pathway [ 95 ]. Multi-omics analysis of esophageal NECs revealed two molecular subtypes based on expression patterns regulated by ASCL1 and NEUROD1 neuroendocrine-lineage transcription factors [ 58 ].…”

BRAF V600E-mutated Colorectal Neuroendocrine Carcinoma Effectively Treated with a Chemotherapy Protocol for BRAF-mutated Metastatic Colorectal Cancer

“…Although the existing strategies for the management of mCRCs have shown promising results, there is a need to develop and clinically evaluate alternate therapies that can help improve the OS of patients with colorectal NECs (9)(10)(11). To this end, we herein report a case of BRAF V600E-mutated colorectal NEC that was successfully managed using FOL-FOXIRI plus Bev and encorafenib plus cetuximab therapy.…”