Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C1658953 (
tumor vasculature
)
2,390
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Tumor cells require vascular supply for their growth, and they express proangiogenic growth factors that promote the formation of vascular networks. Many oncogenic mutations that may potentially lead to tumor angiogenesis have been identified. Somatic mutations in the small GTPase
NRAS
are the most common activating lesions found in human cancer and are generally associated with poor response to standard therapies. However, the mechanisms by which
NRAS
mutations affect tumor angiogenesis are largely unknown. Therefore, we investigated the role of
NRAS
Q61K
oncogene in tumor angiogenesis and analyzed tumors harboring
NRAS
Q61K
for potential sensitivity to a kinase inhibitor. Knock-in of the
NRAS
Q61K
allele in human normal epithelial cells triggered the angiogenic response in these cells. In cancer cells harboring oncogenic
NRAS
, a mitogen-activated protein kinase (MEK) inhibitor down-regulated the extracellular regulated protein kinase (ERK) pathway and inhibited the expression of proangiogenic molecules. In tumor xenografts harboring the
NRAS
Q61K
, the MEK inhibitor extensively modified tumor growth, causing abrogation of angiogenesis. Overall, our results provide a functional link between oncogenic
NRAS
and angiogenesis, and imply that
tumor vasculature
could be indirectly altered by targeting a genetic lesion on which cancer cells are dependent.
...
PMID:Targeting NRAS
Q61K
mutant delays tumor growth and angiogenesis in non-small cell lung cancer. 2846 56
