Gastrointestinal stromal tumor pathophysiology & drug targets

2012 ◽  
pp. 6-17
Author(s):  
Eva Wardelmann
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Drug Targets ◽  
Stromal Tumor

scholarly journals ALK expressed in a gastrointestinal stromal tumor harboring PDGFRA p. D842V mutation:a case report

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jun Fan ◽  
Ming Yang ◽  
Bo Huang ◽  
Zhenkao Wang ◽  
Danju Luo ◽  
...  
Keyword(s):  
Case Report ◽  
Gastrointestinal Stromal Tumor ◽  
Stromal Tumor

scholarly journals Preoperatively diagnosed gastric collision tumor with mixed adenocarcinoma and gastrointestinal stromal tumor: a case report and literature review

2021 ◽  
Author(s):  
Kunihiko Matsuno ◽  
Yoshikazu Kanazawa ◽  
Daisuke Kakinuma ◽  
Nobutoshi Hagiwara ◽  
Fumihiko Ando ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Distal Gastrectomy ◽  
Submucosal Tumor ◽  
Smooth Muscle Actin ◽  
Collision Tumor ◽  
Stromal Tumor ◽  
Lower Body ◽  
Muscle Actin ◽  
First Case ◽  
S 100

AbstractReports of gastric collision tumors, comprising adenocarcinoma and gastrointestinal stromal tumor, are extremely rare. Here, we report the case of a 68-year-old male who was diagnosed with a lower-body, moderately differentiated, tubular-type adenocarcinoma and submucosal tumor and underwent an elective D2 distal gastrectomy. The tumor cells of the gastrointestinal stromal tumor were positive for H-caldesmon and CD117, weakly positive for smooth muscle actin and DOG-1, and negative for desmin, S-100 protein, CD31, and AE1/AE3. The tumor had grown into a mixed form of adenocarcinoma and gastrointestinal stromal tumor. Thus, we report the first case of a preoperatively diagnosed collision tumor in the stomach consisting of adenocarcinoma and gastrointestinal stromal tumor.

scholarly journals Cancer-associated fibroblast secretion of PDGFC promotes gastrointestinal stromal tumor growth and metastasis

Oncogene ◽  
2021 ◽  
Vol 40 (11) ◽  
pp. 1957-1973
Author(s):  
Hyunho Yoon ◽  
Chih-Min Tang ◽  
Sudeep Banerjee ◽  
Mayra Yebra ◽  
Sangkyu Noh ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Tumor Growth ◽  
Gastrointestinal Stromal Tumor ◽  
Single Agent ◽  
Stromal Tumor ◽  
Paracrine Signaling ◽  
Mesenchymal Transition ◽  
Tumor Growth And Metastasis ◽  
Factor C

AbstractTargeted therapies for gastrointestinal stromal tumor (GIST) are modestly effective, but GIST cannot be cured with single agent tyrosine kinase inhibitors. In this study, we sought to identify new therapeutic targets in GIST by investigating the tumor microenvironment. Here, we identified a paracrine signaling network by which cancer-associated fibroblasts (CAFs) drive GIST growth and metastasis. Specifically, CAFs isolated from human tumors were found to produce high levels of platelet-derived growth factor C (PDGFC), which activated PDGFC-PDGFRA signal transduction in GIST cells that regulated the expression of SLUG, an epithelial-mesenchymal transition (EMT) transcription factor and downstream target of PDGFRA signaling. Together, this paracrine induce signal transduction cascade promoted tumor growth and metastasis in vivo. Moreover, in metastatic GIST patients, SLUG expression positively correlated with tumor size and mitotic index. Given that CAF paracrine signaling modulated GIST biology, we directly targeted CAFs with a dual PI3K/mTOR inhibitor, which synergized with imatinib to increase tumor cell killing and in vivo disease response. Taken together, we identified a previously unappreciated cellular target for GIST therapy in order to improve disease control and cure rates.

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