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• W4361944108 abstract "<div>Abstract<p><b>Purpose:</b> Characterization of new anticancer drugs in a few xenograft models derived from established human cancer cell lines frequently results in the discrepancy between preclinical and clinical results. To take the heterogeneity of tumors into consideration more thoroughly, we describe here a preclinical approach that may allow a more rational clinical development of new anticancer drugs.</p><p><b>Experimental Design:</b> We tested Sagopilone, an optimized fully synthetic epothilone, in 22 well-characterized patient-derived non–small cell lung cancer models and correlated results with mutational and genome-wide gene expression analysis.</p><p><b>Results:</b> Response analysis according to clinical trial criteria revealed that Sagopilone induced overall responses in 64% of the xenograft models (14 of 22), with 3 models showing stable disease and 11 models showing partial response. A comparison with response rates for established drugs showed the strong efficacy of Sagopilone in non–small cell lung cancer. In gene expression analyses, Sagopilone induced tubulin isoforms in all tumor samples, but genes related to mitotic arrest only in responder models. Moreover, tumors with high expression of genes involved in cell adhesion/angiogenesis as well as of wild-type <i>TP53</i> were more likely to be resistant to Sagopilone therapy. As suggested by these findings, Sagopilone was combined with Bevacizumab and Sorafenib, drugs targeting vascular endothelial growth factor signaling, in Sagopilone-resistant models and, indeed, antitumor activity could be restored.</p><p><b>Conclusion:</b> Analyses provided here show how preclinical studies can provide hypotheses for the identification of patients who more likely will benefit from new drugs as well as a rationale for combination therapies to be tested in clinical trials. Clin Cancer Res; 16(5); 1452–65</p></div>" @default.
• W4361944108 created "2023-04-05" @default.
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• W4361944108 date "2023-03-31" @default.
• W4361944108 modified "2023-09-25" @default.
• W4361944108 title "Data from Comparative Profiling of the Novel Epothilone, Sagopilone, in Xenografts Derived from Primary Non–Small Cell Lung Cancer" @default.
• W4361944108 doi "https://doi.org/10.1158/1078-0432.c.6518748" @default.
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