SU5416 is a potent inhibitor of hepatocyte growth factor receptor (c-Met) and blocks HGF-induced invasiveness of human HepG2 hepatoma cells

Wang, Si Y.; Chen, Bing; Zhan, Yi Q.; Xu, W.; Li, Chang Y.; Yang, Ri Fu; Zheng, Hong; Yue, P B; Larsen, Steven H.; Sun, Hui; Xiaoming, Yang

doi:10.1016/j.jhep.2004.04.013

Cited by 50 publications

(25 citation statements)

References 28 publications

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“…After the opening of this trial, it was learned that SU5416 inhibits kinases other than VEGFR2 [23][24][25][26][27], increasing the number of possible mechanisms of action. Because only 2 patients consented to pre-and post-treatment research biopsies (both with progression of disease at week 8), there was insufficient data for pharmacodynamic evaluation of SU5416 (data not shown).…”

Section: Discussionmentioning

confidence: 99%

A Phase II study of SU5416 in patients with advanced or recurrent head and neck cancers

et al. 2006

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Section: Discussionmentioning

confidence: 99%

A Phase II study of SU5416 in patients with advanced or recurrent head and neck cancers

et al. 2006

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“…In this context, novel tyrosine kinase inhibitors that block vascular endothelial growth factor receptor, PDGFR and c-kit, like PTK787, may be more active. For example, SU5416 is a potent inhibitor of VEGF receptor, c-kit, PDGFR and hepatocyte growth factor receptor (c-Met) that blocks hepatocyte-growth-factor-induced invasiveness of human HepG2 hepatoma cells in vitro [27]. …”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and Clinical Phase II Trial of Imatinib in Patients with Impaired Liver Function and Advanced Hepatocellular Carcinoma

Eckel¹,

Delius²,

Mayr³

et al. 2005

Oncology

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Objectives: No effective chemotherapy for advanced hepatocellular carcinoma (HCC) exists. Expression of the platelet-derived growth factor receptor (PDGFR) has been demonstrated in HCC, which may derive from hepatic stem cells that express c-kit. The aim of this trial was to evaluate imatinib, a tyrosine kinase inhibitor of PDGFR and c-kit, in patients with advanced HCC and impaired liver function. Patients and Methods: Patients were treated with 400–600 mg imatinib daily. Immunohistochemical staining was performed for PDGFR and c-kit. Response was assessed by CT scans every 8 weeks. For pharmacokinetics studies, 74 plasma samples were assessed. Results: Of the 17 patients enrolled in the study, 15 were evaluable for response. Only 1 tumor was positive for PDGFR and none was positive for c-kit. Grade 3/4 neutropenia occurred in 2 patients (1 had neutropenic fever). There was no objective response, and 5 (33%) patients had stable disease. Median time to treatment failure was 1.8 months in the whole study cohort and 3.7 months in the patients with stable disease. Patients treated with 400 mg imatinib did not significantly differ in pharmacokinetics from patients with chronic myelogenous leukemia (CML). Conclusion: In this small group of patients with advanced, mostly PDGFR- and c-kit-negative HCC, imatinib showed no therapeutic effect. In contrast to CML patients, the pharmacokinetics of imatinib were not significantly affected by impaired liver function.

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“…However, SU5416, another RTK inhibitor, that is chemically related to sunitinib and has similar functional groups, inhibits the activation of HGF/MET in hepatocellular carcinoma. This suggests that sunitinib might be involved in the HGF/MET down-signaling switch off [13]. This case study illustrates the efficacy of sunitinib in metastatic RCC associated with Xp11.2 translocation.…”

Section: Discussionmentioning

confidence: 68%

A case study of metastatic Xp11.2 translocation renal cell carcinoma effectively treated with sunitinib

et al. 2010

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We report a case of Xp11.2 translocation renal cell carcinoma (RCC) whose lung metastases were effectively treated with sunitinib. A 43-year-old woman presenting with upper abdominal pain was diagnosed with a left renal tumor. Laparoscopic left radical nephrectomy was performed. Histopathological examination of the surgical specimen revealed a clear-cell carcinoma of the left kidney. Two years later, multiple lung metastases were detected and the patient was treated daily with 50 mg sunitinib. A computed tomography scan performed after 2 cycles of sunitinib treatment revealed partial regression of these metastases. The partial regression has been maintained for >3 years. In retrospective evaluation of the primary RCC, tumor cells showed strong nuclear staining for transcription factor E3 (TFE3) protein and TFE3 split-fluorescence in-situ hybridization revealed translocation involving the TFE3 gene. These findings strongly support diagnosis of Xp11.2 translocation RCC.

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SU5416 is a potent inhibitor of hepatocyte growth factor receptor (c-Met) and blocks HGF-induced invasiveness of human HepG2 hepatoma cells

Cited by 50 publications

References 28 publications

A Phase II study of SU5416 in patients with advanced or recurrent head and neck cancers

A Phase II study of SU5416 in patients with advanced or recurrent head and neck cancers

Pharmacokinetic and Clinical Phase II Trial of Imatinib in Patients with Impaired Liver Function and Advanced Hepatocellular Carcinoma

A case study of metastatic Xp11.2 translocation renal cell carcinoma effectively treated with sunitinib

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