Thus, the predominance of domain-specific mutations of the same gene in different cancers is mainly a manifestation of the functions driven by those domains, the upstream and downstream signaling processes, and ligand interactions that are intertwined with such domains. When a similar pattern of mutations gets reflected in another form of cancer like ESCC but not in other forms of cancers e.g., lung cancers, there is a possibility of similar interacting ligands or signaling interactions in EGFR.
There have been very few studies on the presence and distribution of EGFR mutations and their relevance in the process of oncogenesis in ESCC. Their presence is rare and insignificant \cite{Guo2016} OR their significance has been less studied. Either way, their copy number is directly related to poor prognosis\cite{Barsouk2019} and changes associated with them, including copy number OR mutations, are one of the changes associated with the development of ESCC \cite{Mandard2000}. Keeping these in the backdrop, we propose that the interacting partners unique to the mutation-specific domains of the EGFR gene in Glioblastoma might match up in functional aspects with those involved in Esophageal Squamous Cell Carcinoma. Given the predominance of ESCCs in the African American population, it would also be interesting to study if the same population matches up in mortality rates in GBM for the same EGFR mutation.
Further investigations in a larger cohort of patient samples are required to validate the role of these mutations in ESCC tumorigenesis as well as their role A.A. population, given their increased predisposition and mortality rates. Identifying these EGFR mutations also opens the potential for targeted therapy in patients with ESCC harboring these rare mutations.
The EGFRvIII mutation lacks the L1 and CR1 domains, which are critical for ligand binding, so it becomes a key driver in tumor progression and is linked to poor prognosis \cite{Shinojima2003}. Therefore, exploring potential shared targets between GBM and ESCC with this mutation profile could lead to the development of effective therapies. A few drug candidates have emerged that specifically target the vIII variants in EGFR \cite{Jain2018} given their pivotal role as a prognostic biomarker. For example, Rindopepimut showed promising results in a phase-II multicenter trial with improved progression-free survival and overall survival metrics \cite{Schuster2015}. These could carry potential use as an off-label treatment for ESCC with EGFRvIII amplification. Alternatively, developing novel therapies that target EGFRvIII or its downstream signaling pathways could be considered for ESCC patients with this mutation profile. Further research and clinical trials are needed to validate these approaches, but they hold promise to improve outcomes for patients with ESCC and EGFRvIII amplification.