KIT/PDGFRA inhibitors for the treatment of gastrointestinal stromal tumors: getting to the gist of the problem

Cicala, Carlo María; Olivares-Rivas, Iván; Aguirre-Carrillo, Jon Ander; Serrano, César

doi:10.1080/13543784.2024.2318317

Expert Opinion on Investigational Drugs

2024

DOI: 10.1080/13543784.2024.2318317

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KIT/PDGFRA inhibitors for the treatment of gastrointestinal stromal tumors: getting to the gist of the problem

Carlo María Cicala,

Iván Olivares-Rivas,

Jon Ander Aguirre-Carrillo

et al.

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2024

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Cited by 3 publications

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Germline variant profiling of CHEK2 sequencing variants in breast cancer patients

McCarthy-Leo,

Baughan,

Dlugas

et al. 2024

Cancer Genetics

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Germline variant profiling of CHEK2 sequencing variants in breast cancer patients

McCarthy-Leo,

Baughan,

Dlugas

et al. 2024

Cancer Genetics

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circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway

Zou,

Tang,

et al. 2024

Sci Rep

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Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are implicated in the development and progression of various tumors. The aim of this study was to investigate the effects of circ_SMA4 in Gastrointestinal Stromal Tumors (GISTs) malignant progression. Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in GISTs. The effect of circ_SMA4 on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo settings. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_SMA4/miR-494-3p/ KIT axis. The results revealed that circ_SMA4 was significantly upregulated in GISTs, and exhibited high diagnostic efficiency with an AUC of 0.9824 (P < 0.01). circ_SMA4 promoted cell proliferation, invasion, migration, while inhibiting apoptosis in GISTs cells, both in vitro and in vivo. Silencing circ_SMA4 partially inhibited GISTs malignant progression. Additionally, circ_SMA4 acted as a competing endogenous RNA (ceRNA) by targeting miR-494-3p, and KIT was identified as a functional gene for miR-494-3p in GISTs. Furthermore, the results confirmed that circ_SMA4/miR-494-3p/ KIT axis plays a role in activating the JAK/STAT signaling pathway in GISTs. Therefore, for the first time, we have identified and emphasized that circ_SMA4 is significantly upregulated and plays an oncogenic role in GISTs by sponging miR-494-3p to activate the KIT/JAK/STAT pathway. These findings underscore circ_SMA4 may serve as a novel diagnostic biomarker and therapeutic target for GISTs. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-73393-w.

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Molecular characteristics and immune microenvironment of gastrointestinal stromal tumours: targets for therapeutic strategies

Yu,

Luo

et al. 2024

Front. Oncol.

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Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours, arising mainly from the interstitial cells of Cajal (ICCs) of the gastrointestinal tract. As radiotherapy and chemotherapy are generally ineffective for GISTs, the current primary treatment is surgical resection. However, surgical resection is not choice for most patients. Therefore, new therapeutic strategies are urgently needed. Targeted therapy, represented by tyrosine kinase inhibitors (TKIs), and immunotherapy, represented by immune checkpoint inhibitor therapies and chimeric antigen receptor T-cell immunotherapy (CAR-T), offer new therapeutic options in GISTs and have shown promising treatment responses. In this review, we summarize the molecular classification and immune microenvironment of GISTs and discuss the corresponding targeted therapy and immunotherapy options. This updated knowledge may provide more options for future therapeutic strategies and applications in GISTs.

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KIT/PDGFRA inhibitors for the treatment of gastrointestinal stromal tumors: getting to the gist of the problem

Cited by 3 publications

References 75 publications

Germline variant profiling of CHEK2 sequencing variants in breast cancer patients

Germline variant profiling of CHEK2 sequencing variants in breast cancer patients

circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway

Molecular characteristics and immune microenvironment of gastrointestinal stromal tumours: targets for therapeutic strategies

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