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Systemic Therapy for Gastrointestinal Stromal Tumor: Current Standards and Emerging Challenges

Gastrointestinal stromal tumor (GIST), though rare, is the most common mesenchymal tumors of the gastrointestinal tract. KIT or PDGFRα mutation plays as an oncogenic driver in the majority of GISTs. Surgical resection is the only curative treatment for localized disease. The discovery of imatinib wi...

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Autores principales: Huang, Wen-Kuan, Wu, Chiao-En, Wang, Shang-Yu, Chang, Ching-Fu, Chou, Wen-Chi, Chen, Jen-Shi, Yeh, Chun-Nan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9402763/
https://www.ncbi.nlm.nih.gov/pubmed/35976553
http://dx.doi.org/10.1007/s11864-022-00996-8
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author Huang, Wen-Kuan
Wu, Chiao-En
Wang, Shang-Yu
Chang, Ching-Fu
Chou, Wen-Chi
Chen, Jen-Shi
Yeh, Chun-Nan
author_facet Huang, Wen-Kuan
Wu, Chiao-En
Wang, Shang-Yu
Chang, Ching-Fu
Chou, Wen-Chi
Chen, Jen-Shi
Yeh, Chun-Nan
author_sort Huang, Wen-Kuan
collection PubMed
description Gastrointestinal stromal tumor (GIST), though rare, is the most common mesenchymal tumors of the gastrointestinal tract. KIT or PDGFRα mutation plays as an oncogenic driver in the majority of GISTs. Surgical resection is the only curative treatment for localized disease. The discovery of imatinib with promising anti-tumor effect and successive tyrosine kinase inhibitors (TKI), including second-line sunitinib and third-line regorafenib, revolutionized the management of advanced and metastatic GIST over the past two decades. Recently, ripretinib and avapritinib were approved for the fourth line setting and for PDGFRA exon 18-mutant GIST in first-line setting, respectively. Despite multi-line TKIs exerted ability of disease control, drug resistance remained an obstacle for preventing rapid disease progression. Experimental TKIs or novel therapeutic targets may further improve treatment efficacy. Immune checkpoint inhibitors such as anti-programmed cell death protein-1 (PD1) and anti-CTL-associated antigen 4 (CTLA-4) showed moderate response in early phase trials composed of heavily pretreated patients. KIT/PDGFRα wild-type GISTs are generally less sensitive to imatinib and late-line TKIs. Recent studies demonstrated that targeting fibroblast growth factor receptor signaling may be a potential target for the wild-type GISTs.
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spelling pubmed-94027632022-08-26 Systemic Therapy for Gastrointestinal Stromal Tumor: Current Standards and Emerging Challenges Huang, Wen-Kuan Wu, Chiao-En Wang, Shang-Yu Chang, Ching-Fu Chou, Wen-Chi Chen, Jen-Shi Yeh, Chun-Nan Curr Treat Options Oncol Sarcoma (SH Okuno, Section Editor) Gastrointestinal stromal tumor (GIST), though rare, is the most common mesenchymal tumors of the gastrointestinal tract. KIT or PDGFRα mutation plays as an oncogenic driver in the majority of GISTs. Surgical resection is the only curative treatment for localized disease. The discovery of imatinib with promising anti-tumor effect and successive tyrosine kinase inhibitors (TKI), including second-line sunitinib and third-line regorafenib, revolutionized the management of advanced and metastatic GIST over the past two decades. Recently, ripretinib and avapritinib were approved for the fourth line setting and for PDGFRA exon 18-mutant GIST in first-line setting, respectively. Despite multi-line TKIs exerted ability of disease control, drug resistance remained an obstacle for preventing rapid disease progression. Experimental TKIs or novel therapeutic targets may further improve treatment efficacy. Immune checkpoint inhibitors such as anti-programmed cell death protein-1 (PD1) and anti-CTL-associated antigen 4 (CTLA-4) showed moderate response in early phase trials composed of heavily pretreated patients. KIT/PDGFRα wild-type GISTs are generally less sensitive to imatinib and late-line TKIs. Recent studies demonstrated that targeting fibroblast growth factor receptor signaling may be a potential target for the wild-type GISTs. Springer US 2022-08-17 2022 /pmc/articles/PMC9402763/ /pubmed/35976553 http://dx.doi.org/10.1007/s11864-022-00996-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Sarcoma (SH Okuno, Section Editor)
Huang, Wen-Kuan
Wu, Chiao-En
Wang, Shang-Yu
Chang, Ching-Fu
Chou, Wen-Chi
Chen, Jen-Shi
Yeh, Chun-Nan
Systemic Therapy for Gastrointestinal Stromal Tumor: Current Standards and Emerging Challenges
title Systemic Therapy for Gastrointestinal Stromal Tumor: Current Standards and Emerging Challenges
title_full Systemic Therapy for Gastrointestinal Stromal Tumor: Current Standards and Emerging Challenges
title_fullStr Systemic Therapy for Gastrointestinal Stromal Tumor: Current Standards and Emerging Challenges
title_full_unstemmed Systemic Therapy for Gastrointestinal Stromal Tumor: Current Standards and Emerging Challenges
title_short Systemic Therapy for Gastrointestinal Stromal Tumor: Current Standards and Emerging Challenges
title_sort systemic therapy for gastrointestinal stromal tumor: current standards and emerging challenges
topic Sarcoma (SH Okuno, Section Editor)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9402763/
https://www.ncbi.nlm.nih.gov/pubmed/35976553
http://dx.doi.org/10.1007/s11864-022-00996-8
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