Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the recent years, the improved understanding of the biological relevance of angiogenesis as a major cancer hallmark led to the development of a heterogeneous group of agents targeting this key process. Among the anti-angiogenic drugs (including monoclonal antibodies such as Bevacizumab, and other molecules with different mechanism of action, such as the vascular disrupting agents Vadimezan), the tyrosine kinase inhibitors (TKIs, Sorafenib, Sunitinib, Pazopanib, and Axitinib), are commonly thought to inhibit angiogenesis through a most rational and promising approach. In this regard, many tyrosine kinase inibitors, such as Sorafenib, are multi-targeted, which allows for the inhibition of those multiple functional pathways which are considered to be critical for both tumor development and progression. Besides, this multi-targeted activity may theoretically increase efficacy but also toxicity. As a member of this group, Sorafenib has already been approved for the treatment of advanced renal cell carcinoma (RCC) and hepatocellular carcinoma not suitable for locoregional treatment, and it is currently under investigation for advanced non small cell lung cancer (NSCLC), either alone or in combination with other biological/cytotoxic agents.
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PMID:Sorafenib for lung cancer: is the "Battle" still open? 2279 3

Klotho was originally characterized as an aging suppressor gene that predisposed Klotho-deficient mice to premature aging-like syndrome. Although Klotho was recently reported to exhibit tumor suppressive properties during various malignant transformations, the functional role and molecular mechanism of Klotho in hepatocarcinogenesis remains poorly understood. In our present study, immunohistochemical Klotho staining levels in a clinical follow-up of 52 hepatoma patients were significantly associated with liver cirrhosis, tumor multiplicity and venous invasion. The overall survival rate of hepatoma patients with high Klotho expression was significantly lower than those patients with low Klotho expression. Moreover, Klotho overexpression increased cellular migration, anchorage-independent growth, and anoikis resistance in hepatoma cells. Klotho overexpression elevated p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase activity inhibition with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor IPA3 treatment reversed anoikis resistance in Klotho-overexpressed hepatoma cells. More importantly, the pivotal significance of upregulated VEGFR2 protein levels mediated by Klotho expression was confirmed by VEGFR2 inhibitor Axitinib and blocking antibody treatment in hepatoma cells. Axitinib treatment sensitized anoikis was reversed by constitutive active mutant PAK1 T423E coexpression in Klotho-overexpressed hepatoma cells. Conversely, knockdown of Klotho reduced VEGFR2/PAK1 dependent anoikis resistance, which could be reversed by PAK1 T423E. These results revealed a novel oncogenic function of Klotho in promoting anoikis resistance via activating VEGFR2/PAK1 signaling, thus facilitating tumor migration and invasion during hepatoma progression, which could provide a putative molecular mechanism for tumor metastasis.
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PMID:Klotho endows hepatoma cells with resistance to anoikis via VEGFR2/PAK1 activation in hepatocellular carcinoma. 2351 76

Hepatocellular carcinoma (HCC) is a common histological class of primary liver cancer with dismal prognosis. Long noncoding RNAs (lncRNAs) are increasingly documented as participators in cancers. Present study aimed to explore the role of long intergenic nonprotein-coding RNA 467 (LINC00467) in HCC. LINC00467 was upregulated in HCC samples in TCGA database, and was confirmed to be elevated in HCC cell lines. Functionally, LINC00467 depletion impeded proliferation and invasion, induced apoptosis, and promoted cellular sensitivity to Axitinib in HCC. Mechanistically, LINC00467 performed as a sponge of microRNA (miR)-509-3p and upregulated the expression of platelet-derived growth factor receptor alpha (PDGFRA) in HCC cells. In conclusion, our study illustrated that LINC00467 promoted proliferation and invasion, impedes apoptosis, and contributed to Axitinib resistance of hepatocellular carcinoma through miR-509-3p/PDGFRA, indicating LINC00467 as a promising biological target for HCC treatment.
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PMID:Knockdown of LINC00467 contributed to Axitinib sensitivity in hepatocellular carcinoma through miR-509-3p/PDGFRA axis. 3222 2