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Receptor Tyrosine Kinases Amplified in Diffuse-Type Gastric Carcinoma: Potential Targeted Therapies and Novel Downstream Effectors

SIMPLE SUMMARY: Diffuse-type gastric carcinoma (DGC) is an aggressive subtype of gastric carcinoma with an extremely poor prognosis due to frequent peritoneal metastasis and high probability of recurrence. Its pathogenesis is poorly understood, and consequently, no effective molecular targeted thera...

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Autores principales: Yamaguchi, Hideki, Nagamura, Yuko, Miyazaki, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367326/
https://www.ncbi.nlm.nih.gov/pubmed/35954414
http://dx.doi.org/10.3390/cancers14153750
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author Yamaguchi, Hideki
Nagamura, Yuko
Miyazaki, Makoto
author_facet Yamaguchi, Hideki
Nagamura, Yuko
Miyazaki, Makoto
author_sort Yamaguchi, Hideki
collection PubMed
description SIMPLE SUMMARY: Diffuse-type gastric carcinoma (DGC) is an aggressive subtype of gastric carcinoma with an extremely poor prognosis due to frequent peritoneal metastasis and high probability of recurrence. Its pathogenesis is poorly understood, and consequently, no effective molecular targeted therapy is available. The importance of oncogenic receptor tyrosine kinase (RTK) signaling has been recently demonstrated in the malignant progression of DGC. In particular, RTK gene amplification appears to accelerate peritoneal metastasis. In this review, we provide an overview of RTK gene amplification in DGC and the potential of related targeted therapies. ABSTRACT: Gastric cancer (GC) is a major cause of cancer-related death worldwide. Patients with an aggressive subtype of GC, known as diffuse-type gastric carcinoma (DGC), have extremely poor prognoses. DGC is characterized by rapid infiltrative growth, massive desmoplastic stroma, frequent peritoneal metastasis, and high probability of recurrence. These clinical features and progression patterns of DGC substantially differ from those of other GC subtypes, suggesting the existence of specific oncogenic signals. The importance of gene amplification and the resulting aberrant activation of receptor tyrosine kinase (RTK) signaling in the malignant progression of DGC is becoming apparent. Here, we review the characteristics of RTK gene amplification in DGC and its importance in peritoneal metastasis. These insights may potentially lead to new targeted therapeutics.
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spelling pubmed-93673262022-08-12 Receptor Tyrosine Kinases Amplified in Diffuse-Type Gastric Carcinoma: Potential Targeted Therapies and Novel Downstream Effectors Yamaguchi, Hideki Nagamura, Yuko Miyazaki, Makoto Cancers (Basel) Review SIMPLE SUMMARY: Diffuse-type gastric carcinoma (DGC) is an aggressive subtype of gastric carcinoma with an extremely poor prognosis due to frequent peritoneal metastasis and high probability of recurrence. Its pathogenesis is poorly understood, and consequently, no effective molecular targeted therapy is available. The importance of oncogenic receptor tyrosine kinase (RTK) signaling has been recently demonstrated in the malignant progression of DGC. In particular, RTK gene amplification appears to accelerate peritoneal metastasis. In this review, we provide an overview of RTK gene amplification in DGC and the potential of related targeted therapies. ABSTRACT: Gastric cancer (GC) is a major cause of cancer-related death worldwide. Patients with an aggressive subtype of GC, known as diffuse-type gastric carcinoma (DGC), have extremely poor prognoses. DGC is characterized by rapid infiltrative growth, massive desmoplastic stroma, frequent peritoneal metastasis, and high probability of recurrence. These clinical features and progression patterns of DGC substantially differ from those of other GC subtypes, suggesting the existence of specific oncogenic signals. The importance of gene amplification and the resulting aberrant activation of receptor tyrosine kinase (RTK) signaling in the malignant progression of DGC is becoming apparent. Here, we review the characteristics of RTK gene amplification in DGC and its importance in peritoneal metastasis. These insights may potentially lead to new targeted therapeutics. MDPI 2022-08-01 /pmc/articles/PMC9367326/ /pubmed/35954414 http://dx.doi.org/10.3390/cancers14153750 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Yamaguchi, Hideki
Nagamura, Yuko
Miyazaki, Makoto
Receptor Tyrosine Kinases Amplified in Diffuse-Type Gastric Carcinoma: Potential Targeted Therapies and Novel Downstream Effectors
title Receptor Tyrosine Kinases Amplified in Diffuse-Type Gastric Carcinoma: Potential Targeted Therapies and Novel Downstream Effectors
title_full Receptor Tyrosine Kinases Amplified in Diffuse-Type Gastric Carcinoma: Potential Targeted Therapies and Novel Downstream Effectors
title_fullStr Receptor Tyrosine Kinases Amplified in Diffuse-Type Gastric Carcinoma: Potential Targeted Therapies and Novel Downstream Effectors
title_full_unstemmed Receptor Tyrosine Kinases Amplified in Diffuse-Type Gastric Carcinoma: Potential Targeted Therapies and Novel Downstream Effectors
title_short Receptor Tyrosine Kinases Amplified in Diffuse-Type Gastric Carcinoma: Potential Targeted Therapies and Novel Downstream Effectors
title_sort receptor tyrosine kinases amplified in diffuse-type gastric carcinoma: potential targeted therapies and novel downstream effectors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367326/
https://www.ncbi.nlm.nih.gov/pubmed/35954414
http://dx.doi.org/10.3390/cancers14153750
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