Advances in Biomarker-Guided Therapies and Epigenetic Approaches for Esophagogastric and Esophageal Cancers

Esophageal cancer (EC) is a highly aggressive malignancy, ranking as the sixth leading cause of cancer-related deaths globally. The two primary histological subtypes are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), each associated with distinct geographic prevalence and risk factors. ESCC is more common in regions like China and Africa, while EAC is predominant in Western countries. Risk factors for ESCC include smoking, alcohol, and dietary habits, whereas EAC is linked to gastroesophageal reflux disease (GERD) and obesity. Early diagnosis and multidisciplinary treatment are critical for improving patient outcomes. Esophageal cancer (EC) remains one of the most lethal cancers worldwide, with a ۹۲% annual mortality rate. The two main subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), continue to have poor prognoses due to late-stage diagnosis and limited screening options. Presently, esophageal biopsy via upper endoscopy is the standard diagnostic approach, but it is invasive and fails to yield comprehensive molecular profiles. Therefore, non-invasive biomarkers, such as liquid biopsies using blood, urine, or saliva, are being investigated for early diagnosis and point-of-care screening. This review discusses the various biomarkers and specimen retrieval techniques being explored for EC diagnosis, focusing on immunohistochemical, blood-based, miRNA, and gene expression profiling. Identifying these biomarkers will help predict prognosis and improve treatment efficacy and survival rates in patients with esophageal cancer. Esophagogastric adenocarcinomas (EGAs) are a diverse group of diseases, both anatomically and molecularly. Several well-established biomarkers, including HER۲, PD-L۱, and microsatellite instability (or mismatch repair protein expression), are currently utilized to individualize treatment for patients. Additionally, emerging biomarkers such as Claudin ۱۸.۲, FGFR۲b, and DKN۰۱ are showing clinical relevance. Claudin ۱۸.۲, in particular, has gained significant traction; the anti-Claudin antibody, zolbetuximab, has demonstrated improved overall survival in biomarker-selected patients with advanced EGA in two phase III clinical trials. Other biomarkers, including FGFR۲b and DKN۰۱, are undergoing validation, with associated therapies being explored in clinical studies. Ongoing efforts to discover novel biomarkers in EGA have enhanced the subclassification of upper GI cancers. These advancements, combined with the strategic use of targeted therapies and immunotherapies, offer promising avenues for improving patient outcomes. The integration of biomarker-guided therapies is set to revolutionize the treatment landscape for EGA, providing more precise and effective interventions for patients. Additionally, the role of epigenetic modifications in cancer therapy is gaining increasing attention. Targeting the epigenome, including DNA methylation and histone modifications, is emerging as a promising therapeutic approach. Several epigenetic drugs are in clinical trials, offering new avenues for combination therapies. Moreover, mitochondrial mutations and epigenetic regulation also play critical roles in cancer progression and treatment responses, opening up new therapeutic strategies.

کلیدواژه ها:

Esophageal cancer (EC) ، Immunohistochemical markers ، Epigenetic modifications ، Targeted therapies ، Non-invasive diagnosis