scholarly journals Gastrointestinal Stromal Tumors (GIST): A Prospective Analysis and an Update on Biomarkers and Current Treatment Concepts

2015 ◽  
Vol 7s1 ◽  
pp. BIC.S25045 ◽  
Author(s):  
Anna Koumarianou ◽  
Panagiota Economopoulou ◽  
Panagiotis Katsaounis ◽  
Konstantinos Laschos ◽  
Petroula Arapantoni-Dadioti ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitor ◽  
Treatment Guidelines ◽  
Growth Factor Receptor ◽  
Current Treatment ◽  
University Hospital ◽  
Stromal Tumors ◽  
Outpatient Unit ◽  
Factor Receptor Alpha ◽  
Metastatic Setting

Gastrointestinal Stromal tumors (GIST) are the most common sarcomas of the gastrointestinal tract, with transformation typically driven by activating mutations of cKIT and less commonly platelet-derived growth factor receptor alpha (PDGFRA). Successful targeting of tyrosine-protein kinase Kit with imatinib, a tyrosine kinase inhibitor, has had a major impact in the survival of patients with GIST in both the adjuvant and metastatic setting. A recent modification of treatment guidelines for patients with localized, high-risk GIST extended the adjuvant treatment duration from 1 year to 3 years. In this paper, we review the clinical data of patients with GIST treated in the Oncology Outpatient Unit of “Attikon” University Hospital and aim to assess which patients are eligible for prolongation of adjuvant imatinib therapy as currently suggested by treatment recommendations.

PDGFRA Mutations in Gastrointestinal Stromal Tumors: Frequency, Spectrum and In Vitro Sensitivity to Imatinib

2005 ◽  
Vol 23 (23) ◽  
pp. 5357-5364 ◽  
Author(s):  
Christopher L. Corless ◽  
Arin Schroeder ◽  
Diana Griffith ◽  
Ajia Town ◽  
Laura McGreevey ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
High Performance ◽  
Kinase Inhibitor ◽  
Direct Sequencing ◽  
Mutation Screening ◽  
Growth Factor Receptor ◽  
Stromal Tumors ◽  
Pdgfra Mutation ◽  
Factor Receptor Alpha

Purpose Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT tyrosine kinase, which is a target for the kinase inhibitor imatinib. A subset of GISTs, however, contains mutations in the homologous kinase platelet derived growth factor receptor alpha (PDGFRA), and the most common of these mutations is resistant to imatinib in vitro. Little is known of the other types of PDGFRA mutations that occur in GISTs. Materials and Methods We determined the KIT and PDGFRA mutation status of 1,105 unique GISTs using a combination of denaturing high-performance liquid chromatography and direct sequencing. Results There were 80 tumors (7.2%) with a PDGFRA mutation: 66 in exon 18, 11 in exon 12, and three in exon 14. Transient expression of representative PDGFRA isoforms in CHO cells revealed imatinib sensitivity of exon 12 mutations (SPDHE566-571R and insertion ER561-562) and an exon 14 substitution (N659K). However, most isoforms with a substitution involving codon D842 in exon 18 (D842V, RD841-842KI, DI842-843IM) were resistant to the drug, with the exception of D842Y. Interestingly, other mutations in exon 18 (D846Y, N848K, Y849K and HDSN845-848P) were all imatinib sensitive. Proliferation studies with BA/F3 cell lines stably expressing selected PDGFRA mutant isoforms supported these findings. Conclusion Including our cases, there are 289 reported PDGFRA-mutant GISTs, of which 181 (62.6%) had the imatinib-resistant substitution D842V. However, our findings suggest that more than one third of GISTs with PDGFRA mutations may respond to imatinib and that mutation screening may be helpful in the management of these tumors.

scholarly journals A Malignant Gastrointestinal Stromal Tumor of the Gallbladder Immunoreactive for PDGFRA and Negative for CD 117 Antigen (c-KIT)

HPB Surgery ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Athanasios Petrou ◽  
Pari Alexandrou ◽  
Alexandros Papalambros ◽  
Angelica Saetta ◽  
Paraskevi Fragkou ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Gastrointestinal Stromal Tumors ◽  
Growth Factor Receptor ◽  
Stromal Tumor ◽  
Platelet Derived Growth Factor ◽  
Stromal Tumors ◽  
Cd 117 ◽  
Factor Receptor Alpha ◽  
Malignant Gists ◽  
First Time

Gastrointestinal stromal tumors (GISTs) compose the largest category of well-recognized nonepithelial neoplasms of the gastrointestinal tract (GI). GISTs of the gallbladder are extremely rare tumors. Only four malignant, two benign and one GIST-like tumor of the gall bladder have ever been described. The four malignant GISTs were all positive for CD 117 antigen (c-kit). We present for the first time a malignant gastrointestinal stromal tumor of the gallbladder, immunoreactive for platelet-derived growth factor receptor alpha (PDGFRA) and negative for CD 117 antigen (c-KIT).

scholarly journals Gastrointestinal Stromal Tumors: Molecular Mechanisms and Targeted Therapies

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Erinn Downs-Kelly ◽  
Brian P. Rubin
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Clinicopathological Features ◽  
Platelet Derived Growth Factor ◽  
Clinical Behavior ◽  
Stromal Tumors ◽  
Mesenchymal Neoplasms ◽  
Factor Receptor Alpha

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and are diverse not only in their clinical behavior but also in their histologic appearance. GISTs are insensitive to conventional sarcoma chemotherapy and radiation. However GISTs are sensitive to small-molecule tyrosine kinase inhibitors as 85–90% of GISTs have KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutations, which drive tumorigenesis. This review will briefly touch on the clinicopathological features of GIST, while the majority of the review will focus on the clinical and treatment ramifications of KIT and PDGFRA mutations found in GIST.

scholarly journals BRD9 inhibition promotes PUMA-dependent apoptosis and augments the effect of imatinib in gastrointestinal stromal tumors

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Jianfeng Mu ◽  
Xuezeng Sun ◽  
Zhipeng Zhao ◽  
Hao Sun ◽  
Pengda Sun
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Cellular Proliferation ◽  
Growth Factor Receptor ◽  
Mechanism Study ◽  
Baf Complex ◽  
Stromal Tumors ◽  
Factor Receptor Alpha ◽  
Gsk 3Β

AbstractGastrointestinal stromal tumors (GISTs) are primarily characterized by activating mutations of tyrosine kinase or platelet-derived growth factor receptor alpha. Although the revolutionary therapeutic outcomes of imatinib are well known, the long-term benefits of imatinib are still unclear. The effects of BRD9, a recently identified subunit of noncanonical BAF complex (ncBAF) chromatin remodeling complexes, in GISTs are not clear. In the current study, we evaluated the functional role of BRD9 in GIST progression. Our findings demonstrated that the expression of BRD9 was upregulated in GIST tissues. The downregulation or inhibition of BRD9 could significantly reduce cellular proliferation, and facilitates apoptosis in GISTs. BRD9 inhibition could promote PUMA-dependent apoptosis in GISTs and enhance imatinib activity in vitro and in vivo. BRD9 inhibition synergizes with imatinib in GISTs by inducing PUMA upregulation. Mechanism study revealed that BRD9 inhibition promotes PUMA induction via the TUFT1/AKT/GSK-3β/p65 axis. Furthermore, imatinib also upregulates PUMA by targeting AKT/GSK-3β/p65 axis. In conclusion, our results indicated that BRD9 plays a key role in the progression of GISTs. Inhibition of BRD9 is a novel therapeutic strategy in GISTs treated alone or in combination with imatinib.

scholarly journals Gastrointestinal Stromal Tumors—A Mini Review

2021 ◽  
Vol 11 (8) ◽  
pp. 694
Author(s):  
Gina Gheorghe ◽  
Nicolae Bacalbasa ◽  
Gabriela Ceobanu ◽  
Madalina Ilie ◽  
Valentin Enache ◽  
...  
Keyword(s):  
Digestive Tract ◽  
Gastrointestinal Stromal Tumors ◽  
Histopathological Examination ◽  
Correct Diagnosis ◽  
Growth Factor Receptor ◽  
Risk Category ◽  
Genetic Syndromes ◽  
Stromal Tumors ◽  
Factor Receptor Alpha ◽  
Potentially Malignant

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. They are potentially malignant, and have an unpredictable evolution. The origin of these tumors is in the interstitial cells of Cajal, which are cells that are interposed between the intramural neurons and the smooth muscle cells of the digestive tract. GISTs are characterized by mutations in the gene c-Kit, but also other mutations, such as those of the platelet-derived growth factor receptor alpha. The most common locations of these tumors are the stomach and small intestine, although they can occur at any level of the digestive tract and occasionally in the omentum, mesentery and peritoneum. Most cases of GISTs are sporadic, and about 5% of cases are part of family genetic syndromes. The correct diagnosis of GIST is determined by histopathological examination and immunohistochemistry. According to histopathology, there are three main types of GISTs: spindle cell type, epithelioid type and mixed type. The therapeutic management of GIST includes surgery, endoscopic treatment and chemotherapy. The prognosis of patients with GIST varies depending on a number of factors, such as risk category, GIST stage, treatment applied and recurrence after treatment.

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