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Review

Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors

by
Maria Teresa Masucci
1,*,
Maria Letizia Motti
1,2,
Michele Minopoli
1,
Gioconda Di Carluccio
1 and
Maria Vincenza Carriero
1
1
Preclinical Models of Tumor Progression Unit, Istituto Nazionale Tumori IRCCS ‘Fondazione G. Pascale’, 80131 Naples, Italy
2
Department of Movement Sciences and Wellbeing, University “Parthenope”, 80133 Naples, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(7), 6026; https://doi.org/10.3390/ijms24076026
Submission received: 28 February 2023 / Revised: 17 March 2023 / Accepted: 19 March 2023 / Published: 23 March 2023
(This article belongs to the Special Issue New Strategies in Therapeutic Targets of Sarcoma: Translational Implications 2.0)
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Abstract

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-KIT encoding the tyrosine kinase receptor (TKR) known as KIT and in the platelet-derived growth factor-alpha receptor (PDGFRA) genes. Approved therapeutics are orally available as tyrosine kinase inhibitors (TKIs) targeting KIT and/or PDGFRA oncogenic activation. Among these, imatinib 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 KIT 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.
Keywords: gastrointestinal stromal tumors; drug resistance; targeted therapies; biomarkers gastrointestinal stromal tumors; drug resistance; targeted therapies; biomarkers

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MDPI and ACS Style

Masucci, M.T.; Motti, M.L.; Minopoli, M.; Di Carluccio, G.; Carriero, M.V. Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors. Int. J. Mol. Sci. 2023, 24, 6026. https://doi.org/10.3390/ijms24076026

AMA Style

Masucci MT, Motti ML, Minopoli M, Di Carluccio G, Carriero MV. Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors. International Journal of Molecular Sciences. 2023; 24(7):6026. https://doi.org/10.3390/ijms24076026

Chicago/Turabian Style

Masucci, Maria Teresa, Maria Letizia Motti, Michele Minopoli, Gioconda Di Carluccio, and Maria Vincenza Carriero. 2023. "Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors" International Journal of Molecular Sciences 24, no. 7: 6026. https://doi.org/10.3390/ijms24076026

APA Style

Masucci, M. T., Motti, M. L., Minopoli, M., Di Carluccio, G., & Carriero, M. V. (2023). Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors. International Journal of Molecular Sciences, 24(7), 6026. https://doi.org/10.3390/ijms24076026

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