Patrick S Plum1, Alexander Quaas2, Hakan Alakus3, Christiane J Bruns3. 1. Klinik und Poliklinik für Allgemein‑, Viszeral‑, Tumor- und Transplantationschirurgie, Uniklinik Köln, Kerpener Straße 62, 50937, Köln, Deutschland. Patrick.plum@uk-koeln.de. 2. Institut für Pathologie, Uniklinik Köln, Köln, Deutschland. 3. Klinik und Poliklinik für Allgemein‑, Viszeral‑, Tumor- und Transplantationschirurgie, Uniklinik Köln, Kerpener Straße 62, 50937, Köln, Deutschland.
Abstract
BACKGROUND: In the recent past tumors of the upper gastrointestinal (GI) tract, e.g. esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and gastric adenocarcinoma, have been increasingly characterized by molecular genetics. The resulting subtypes provide potential targets for novel targeted treatment based on the biological characteristics. OBJECTIVE: This article summarizes the current state of molecular subtyping in all three tumor entities and the individualized treatment strategies derived from these categories are discussed. MATERIAL AND METHODS: A selective literature search was performed focusing on molecular subtyping, current targeted treatment and the impact on the oncological treatment concepts. Databases such as PubMed were used. RESULTS: Based on molecular characteristics ESCC is nowadays categorized into three subtypes. Genetically, at least one subgroup resembles oropharyngeal carcinomas rather than those of the upper GI tract. In contrast, EAC is characterized by its high tumor burden and large chromosomal instability. In gastric carcinoma 4 subtypes are distinguished: 1) Epstein-Barr virus (EBV) positive, 2) microsatellite instability (MSI), 3) genomically stable (GS) and 4) chromosomally unstable (CIN) tumors. CONCLUSION: To date, only a few targeted therapeutic options have been successfully transferred into daily routine derived from the genetic characterization of the three tumor entities. These include selective ERBB2 inhibition, immunotherapy using PD-L1 inhibition or combined blockade of ERBB2/VEGF.
BACKGROUND: In the recent past tumors of the upper gastrointestinal (GI) tract, e.g. esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and gastric adenocarcinoma, have been increasingly characterized by molecular genetics. The resulting subtypes provide potential targets for novel targeted treatment based on the biological characteristics. OBJECTIVE: This article summarizes the current state of molecular subtyping in all three tumor entities and the individualized treatment strategies derived from these categories are discussed. MATERIAL AND METHODS: A selective literature search was performed focusing on molecular subtyping, current targeted treatment and the impact on the oncological treatment concepts. Databases such as PubMed were used. RESULTS: Based on molecular characteristics ESCC is nowadays categorized into three subtypes. Genetically, at least one subgroup resembles oropharyngeal carcinomas rather than those of the upper GI tract. In contrast, EAC is characterized by its high tumor burden and large chromosomal instability. In gastric carcinoma 4 subtypes are distinguished: 1) Epstein-Barr virus (EBV) positive, 2) microsatellite instability (MSI), 3) genomically stable (GS) and 4) chromosomally unstable (CIN) tumors. CONCLUSION: To date, only a few targeted therapeutic options have been successfully transferred into daily routine derived from the genetic characterization of the three tumor entities. These include selective ERBB2 inhibition, immunotherapy using PD-L1 inhibition or combined blockade of ERBB2/VEGF.
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