Abstract
A recent study identified two EGFR gene mutations commonly found in the EGFR gene for glioblastoma multiforme (GBM), EGFRvIII, and EGFRvIVa in two of ten African American patients with esophageal squamous cell carcinoma (ESCC). EGFRvIII mutation is a key driver in tumor progression and is associated with a poor prognosis as it lacks the L1 and CR1 domains, which are crucial for ligand binding. Herein a discussion is presented on the identification of these rare and clinically significant mutations in ESCC patients, which raises important questions about the functional implications of these mutations, the feasibility of observational clinical trials, and the use of off-label EGFR inhibitors.
Keywords:
EGFR, Esophageal Squamous Cell Carcinoma, Glioblastoma Multiforme, Genomics, Targeted Therapy
Introduction
Esophageal cancer has a strikingly low survival rate, mainly due to the lack of diagnostic markers for early detection and effective therapies. Their incidence rate in the U.S. alone still remains skewed in the disfavor of the African American population. According to recent trends from the NCI SEER data \cite{application}, the incidence rates of individuals in African Americans (AA) diagnosed with esophageal squamous cell carcinoma (ESCC) are nearly twice as much as combined rates from all other races (Fig 1). Though the incidence rates have witnessed a remarkable decline in the AA population and their predisposition to ESCC, the resulting mortality rates still remain high compared to the rest of the population in the US.
Recently, a study by whole-genome sequencing was carried out in matched tumor and normal tissues from 10 African American patients to identify tumor-specific genomic abnormalities\cite{Erkizan2021}. Two interesting mutations were identified in the EGFR gene that is typically found in the EGFR gene for Glioblastoma Multiforme (GBM), EGFRvIII, and EGFRvIVa. These findings raise important questions about the functional implications of these mutations between these two cancers, the feasibility of observational clinical trials, and the use of off-label EGFR inhibitors; a discussion of which is presented below.