Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors
Gastrointestinal stromal tumors (GISTs) are the most common malignant mesenchymal neoplasms of the gastrointestinal tract. The gold standard for the diagnosis of GISTs is morphologic analysis with an immunohistochemical evaluation plus genomic profiling to assess the mutational status of lesions. Th...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6026 |
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| author | Maria Teresa Masucci Maria Letizia Motti Michele Minopoli Gioconda Di Carluccio Maria Vincenza Carriero |
| author_facet | Maria Teresa Masucci Maria Letizia Motti Michele Minopoli Gioconda Di Carluccio Maria Vincenza Carriero |
| author_sort | Maria Teresa Masucci |
| collection | DOAJ |
| description | Gastrointestinal stromal tumors (GISTs) are the most common malignant mesenchymal neoplasms of the gastrointestinal tract. The gold standard for the diagnosis of GISTs is morphologic analysis with an immunohistochemical evaluation plus genomic profiling to assess the mutational status of lesions. The majority of GISTs are driven by gain-of-function mutations in the proto-oncogene c-<i>KIT</i> encoding the tyrosine kinase receptor (TKR) known as KIT and in the platelet-derived growth factor-alpha receptor (<i>PDGFRA</i>) genes. Approved therapeutics are orally available as tyrosine kinase inhibitors (TKIs) targeting KIT and/or PDGFRA oncogenic activation. Among these, <i>imatinib</i> has changed the management of patients with unresectable or metastatic GISTs, improving their survival time and delaying disease progression. Nevertheless, the majority of patients with GISTs experience disease progression after 2–3 years of imatinib therapy due to the development of secondary <i>KIT</i> mutations. Today, based on the identification of new driving oncogenic mutations, targeted therapy and precision medicine are regarded as the new frontiers for GISTs. This article reviews the most important mutations in GISTs and highlights their importance in the current understanding and treatment options of GISTs, with an emphasis on the most recent clinical trials. |
| first_indexed | 2024-03-11T05:36:48Z |
| format | Article |
| id | doaj.art-5eafe20ae379487cbaeeafe117c27707 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:36:48Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5eafe20ae379487cbaeeafe117c277072023-11-17T16:45:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247602610.3390/ijms24076026Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal TumorsMaria Teresa Masucci0Maria Letizia Motti1Michele Minopoli2Gioconda Di Carluccio3Maria Vincenza Carriero4Preclinical Models of Tumor Progression Unit, Istituto Nazionale Tumori IRCCS ‘Fondazione G. Pascale’, 80131 Naples, ItalyPreclinical Models of Tumor Progression Unit, Istituto Nazionale Tumori IRCCS ‘Fondazione G. Pascale’, 80131 Naples, ItalyPreclinical Models of Tumor Progression Unit, Istituto Nazionale Tumori IRCCS ‘Fondazione G. Pascale’, 80131 Naples, ItalyPreclinical Models of Tumor Progression Unit, Istituto Nazionale Tumori IRCCS ‘Fondazione G. Pascale’, 80131 Naples, ItalyPreclinical Models of Tumor Progression Unit, Istituto Nazionale Tumori IRCCS ‘Fondazione G. Pascale’, 80131 Naples, ItalyGastrointestinal stromal tumors (GISTs) are the most common malignant mesenchymal neoplasms of the gastrointestinal tract. The gold standard for the diagnosis of GISTs is morphologic analysis with an immunohistochemical evaluation plus genomic profiling to assess the mutational status of lesions. The majority of GISTs are driven by gain-of-function mutations in the proto-oncogene c-<i>KIT</i> encoding the tyrosine kinase receptor (TKR) known as KIT and in the platelet-derived growth factor-alpha receptor (<i>PDGFRA</i>) genes. Approved therapeutics are orally available as tyrosine kinase inhibitors (TKIs) targeting KIT and/or PDGFRA oncogenic activation. Among these, <i>imatinib</i> has changed the management of patients with unresectable or metastatic GISTs, improving their survival time and delaying disease progression. Nevertheless, the majority of patients with GISTs experience disease progression after 2–3 years of imatinib therapy due to the development of secondary <i>KIT</i> mutations. Today, based on the identification of new driving oncogenic mutations, targeted therapy and precision medicine are regarded as the new frontiers for GISTs. This article reviews the most important mutations in GISTs and highlights their importance in the current understanding and treatment options of GISTs, with an emphasis on the most recent clinical trials.https://www.mdpi.com/1422-0067/24/7/6026gastrointestinal stromal tumorsdrug resistancetargeted therapiesbiomarkers |
| spellingShingle | Maria Teresa Masucci Maria Letizia Motti Michele Minopoli Gioconda Di Carluccio Maria Vincenza Carriero Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors International Journal of Molecular Sciences gastrointestinal stromal tumors drug resistance targeted therapies biomarkers |
| title | Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors |
| title_full | Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors |
| title_fullStr | Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors |
| title_full_unstemmed | Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors |
| title_short | Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors |
| title_sort | emerging targeted therapeutic strategies to overcome imatinib resistance of gastrointestinal stromal tumors |
| topic | gastrointestinal stromal tumors drug resistance targeted therapies biomarkers |
| url | https://www.mdpi.com/1422-0067/24/7/6026 |
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