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Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants

  1. Top of page
  2. Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants
  3. Ganglioside GD3 induces convergence and synergism of adhesion and hepatocyte growth factor/Met signals in melanomas
  4. NRD1, which encodes nardilysin protein, promotes esophageal cancer cell invasion through induction of MMP2 and MMP3 expression
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Page 117–25

The pathogenesis of up to 80% of all gastrointestinal stromal tumors (GISTs) result from an activation of the stem cell factor receptor KIT. A tyrosine kinase inhibitor, imatinib mesylate, has been used to treat these tumors. Unfortunately, a number of GISTs show resistance to imatinib, and secondary drugs must be used. In this study, Zhao and coworkers explored the possibility that flumatinib, an alternative tyrosine kinase inhibitor, might be able to overcome many of the drug-resistant strains of GISTs. Through both in vivo and in vitro studies these researchers determined that flumatinib had superior efficacy when compared to imatinib or sunitinib (another tyrosine kinase inhibitor) in GISTs with a secondary mutation in the KIT activation loop. This study offers great promise for eventual clinical utility in patients with multidrug-resistant GISTs, as well as other KIT mutation-associated tumors.doi:10.1111/cas.12320

Ganglioside GD3 induces convergence and synergism of adhesion and hepatocyte growth factor/Met signals in melanomas

  1. Top of page
  2. Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants
  3. Ganglioside GD3 induces convergence and synergism of adhesion and hepatocyte growth factor/Met signals in melanomas
  4. NRD1, which encodes nardilysin protein, promotes esophageal cancer cell invasion through induction of MMP2 and MMP3 expression
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Page 52–63

Melanoma tends to be an aggressive neoplasm with high metastatic potential, yet the molecular pathways that lead to these behaviors are not ful o apoptosis. Prior work has shown that Akt and Erk family proteins are involved in melanoma cell growth, along with hepatocyte growth factor/Met-mediated signaling and cell adhesion complexes. The authors hypothesized that the ganglioside GD3 was involved in promoting these pathways. Their results indicated that hepatocyte growth factor/Met-mediated signaling was enhanced by GD3, but only in the presence of cell adhesion. They went on to show that these cells were also more resistant to chemically induced apoptosis. These results revealed the linkage of two important cellular processes by the ganglioside GD3.doi:10.1111/cas.12310

NRD1, which encodes nardilysin protein, promotes esophageal cancer cell invasion through induction of MMP2 and MMP3 expression

  1. Top of page
  2. Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants
  3. Ganglioside GD3 induces convergence and synergism of adhesion and hepatocyte growth factor/Met signals in melanomas
  4. NRD1, which encodes nardilysin protein, promotes esophageal cancer cell invasion through induction of MMP2 and MMP3 expression
Thumbnail image of

Page 134–40

Esophageal carcinoma is one of the most common malignancies worldwide and has a poor overall prognosis. Tumor stage is a reliable prognostic factor, but molecular markers that may predict outcomes are under investigation. In their exciting work, Uraoka and colleagues analyzed tissue samples from patients with squamous cell carcinoma of the esophagus for gene expression that could predict outcomes. They found that activation of the gene encoding the nardilysin protein, NRD1, correlated with increased tumor invasiveness, nodal status, and overall prognosis. The authors ambitiously went on to show that knockdown of the nardilysin gene using siRNA can reduce tumor invasiveness. These results advance the understanding of esophageal cancer and indicate that the NRD1 gene is an important prognostic marker, and perhaps therapeutic target, in this disease.doi:10.1111/cas.12316