Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ROS1 protein-tyrosine kinase fusion proteins are expressed in 1-2% of non-small cell lung cancers. The ROS1 fusion partners include CD74, CCDC6, EZR, FIG, KDELR2, LRIG3, MSN, SDC4, SLC34A2, TMEM106B, TMP3, and TPD52L1. Physiological ROS1 is closely related to the ALK, LTK, and insulin receptor protein-tyrosine kinases. ROS1 is a so-called orphan receptor because the identity of its activating ligand, if any, is unknown. The receptor is expressed during development, but little is expressed in adults and its physiological function is unknown. The human ROS1 gene encodes 2347 amino acid residues and ROS1 is the largest protein-tyrosine kinase receptor protein. Unlike the ALK fusion proteins that are activated by the dimerization induced by their amino-terminal portions, the amino-terminal domains of several of its fusion proteins including CD74 apparently lack the ability to induce dimerization so that the mechanism of constitutive protein kinase activation is unknown. Downstream signaling from the ROS1 fusion protein leads to the activation of the Ras/Raf/MEK/ERK1/2 cell proliferation module, the phosphatidyl inositol 3-kinase cell survival pathway, and the Vav3 cell migration pathway. Moreover, several of the ROS1 fusion proteins are implicated in the pathogenesis of a very small proportion of other cancers including glioblastoma, angiosarcoma, and cholangiocarcinoma as well as ovarian, gastric, and colorectal carcinomas. The occurrence of oncogenic ROS1 fusion proteins, particularly in non-small cell lung cancer, has fostered considerable interest in the development of ROS1 inhibitors. Although the percentage of lung cancers driven by ROS1 fusion proteins is low, owing to the large number of new cases of non-small cell lung cancer per year, the number of new cases of ROS1-positive lung cancers is significant and ranges from 2000 to 4000 per year in the United States and 10,000-15,000 worldwide. Crizotinib was the first inhibitor approved by the US Food and Drug Administration for the treatment of ROS1-positive non-small cell lung cancer in 2016. Other drugs that are in clinical trials for the treatment of these lung cancers include ceritinib, cabozantinib, entrectinib, and lorlatinib. Crizotinib forms a complex within the front cleft between the small and large lobes of an active ROS1 protein-kinase domain and it is classified as type I inhibitor.
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PMID:ROS1 protein-tyrosine kinase inhibitors in the treatment of ROS1 fusion protein-driven non-small cell lung cancers. 2846 16

Glioblastoma (GBM) is one of the most common malignancies of the central nervous system, and the Isocitrate Dehydrogenase (IDH) mutation status of GBM has been recognized as a critical prognostic indicator. However, the molecular mechanism underlying the GBM with different IDH mutation status is still not unclear. In this study, a total of 353 DEGs including 207 up-regulated and 146 down-regulated were screened from multiple GBM data sets. Moreover, the biological processes and pathways enriched by DEGs were mainly associated with tumor progression, especially invasion and migration. Then, eight hub genes, including SDC4, SERPINE1, TNC, THBS1, COL1A1, CXCL8, TIMP1 and VEGFA, were selected from a PPI network. Finally, core genes, SERPINE1 and TIMP1, were identified from hub genes by survival analysis and sample validation. Overall, in this study, we revealed underlying molecular mechanisms in GBMs with different IDH mutation status and identified core genes that could be potential markers and targets for diagnosis and treatment of GBMs.
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PMID:Identification of two core genes in glioblastomas with different isocitrate dehydrogenase mutation status. 3291 3