325 research outputs found
Spotlight on afatinib and its potential in the treatment of squamous cell lung cancer: the evidence so far
No full textYijun Xu,1,2 Vivianne W Ding,1 Hong Zhang,2 Xun Zhang,2 David Jablons,1 Biao He1 1Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA; 2Tianjin Chest Hospital, Tianjin, People’s Republic of China Abstract: Compared to adenocarcinoma, fewer effective treatment options are available for advanced or metastatic squamous cell carcinoma (SCC) of the lung. Afatinib is an orally administered, irreversible EGFR antagonist. As a second-generation tyrosine kinase inhibitor, it has been applied in the treatment of patients with EGFR-mutant non-small-cell lung cancer. Recently, several clinical trials have shown that afatinib leads to a significant improvement in progression-free survival and overall survival of patients with SCC. Moving forward, afatinib should be one of the options among tyrosine kinase inhibitors, monoclonal antibodies, and cytotoxicity chemotherapy drugs for SCC. Keywords: afatinib, squamous cell carcinoma, EGFR, tyrosine kinase inhibitor, non-small-cell lung cancer, ErbB 
Y1-13: Assessment of mediastinal disease: invasive approach vs PET: the case for invasive techniques
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MK256 is a novel CDK8 inhibitor with potent antitumor activity in AML through downregulation of the STAT pathway
No full textAcute myeloid leukemia (AML) is the most lethal form of AML due to disease relapse. Cyclin dependent kinase 8 (CDK8) is a serine/threonine kinase that belongs to the family of Cyclin-dependent kinases and is an emerging target for the treatment of AML. MK256, a potent, selective, and orally available CDK8 inhibitor was developed to target AML. We sought to examine the anticancer effect of MK256 on AML. In CD34+/CD38- leukemia stem cells, we found that MK256 induced differentiation and maturation. Treatment of MK256 inhibited proliferation of AML cell lines. Further studies of the inhibitory effect suggested that MK256 not only downregulated phosphorylated STAT1(S727) and STAT5(S726), but also lowered mRNA expressions of MCL-1 and CCL2 in AML cell lines. Efficacy of MK256 was shown in MOLM-14 xenograft models, and the inhibitory effect on phosphorylated STAT1(S727) and STAT5(S726) with treatment of MK256 was observed in vivo. Pharmacologic dynamics study of MK256 in MOLM-14 xenograft models showed dose-dependent inhibition of the STAT pathway. Both in vitro and in vivo studies suggested that MK256 could effectively downregulate the STAT pathway. In vitro ADME, pharmacological kinetics, and toxicity of MK256 were profiled to evaluate the drug properties of MK256. Our results show that MK256 is a novel CDK8 inhibitor with a desirable efficacy and safety profile and has great potential to be a promising drug candidate for AML through regulating the STAT pathway
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An alternative way to initiate Notch1 signaling in non-small cell lung cancer.
No full textNon-small cell lung cancer (NSCLC) cells activate Notch1 signaling to promote cell proliferation and facilitate their survival. It now emerges that endothelial Delta-like ligand 4 (Dll4) may mediate Notch1 activation and inhibit tumor cell growth
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