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• W2343122424 abstract "14519 Background: Bevacizumab (BV), an AB against VEGF, was recently approved in combination regimens for metastatic colon, lung and renal cancer patients. Cetuximab (CTX) directed aginst EGFR was approved in combinations in metastatic colon and in head and neck cancers. We investigated the hypothesis that correlating drug response with gene expression would identify specific gene signatures which predict the response of individual tumors. Methods: For 220 patient derived solid tumor models growing sc in nude mice gene expression profiles of ∼38k genes were determined using the Affymetrix HG-U133 plus 2.0 chip. In a previous study we have demonstrated a high correct correlation of in-vivo xenograft testings for standard agents compared to the responses in the 80 donor patients. Now BV was investigated in 72 xenografts applied iv at 40 mg/kg on day 0, and 20mg/kg/d on day 7 and 14, respectively, when the tumors reached ∼100 mm³. Results: For BV using a T/C of <34% as cut-off for activity 29% (21/72) of all tumors were sensitive, 12/34 NSCLC, 4/18 colon, 3/10 breast and 2/10 renal cancers. The bioinformatic analysis yielded an optimal signature consisting of 35 genes. The 72 tests were randomly divided into a training and a testing set (47 and 25 tumors). The gene signature was validated using the leave-one-out cross- validation (LOOCV) and in the independent testing set. In the LOOCV 15/47 tumors were predicted to respond from which in the real testings 10 responded which resulted in an increase of response rate from 30% (14/47) to 67%. From the predicted 32 non-responders 28 (88%) were resistant in real testings. In the independent testing set the correct prediction was 71% for the predicted responders and 89% for the non- responders. From the 35 genes 21 are associated with angiogenesis. In a similar study a gene signature was determined for CTX consisting of 26 genes. In 54 tumors (colon, H+N, NSCLC) a response rate of 24% was obtained in random vs. 61% in gene signature guided testing, respectively. The correct prediction for non-response was 94% for CTX. Conclusions: Specific gene signatures predicted responsiveness and resistance against BV and CTX. They are now being tested in fresh tumor samples from cancer patients. No significant financial relationships to disclose." @default.
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• W2343122424 date "2008-05-20" @default.
• W2343122424 modified "2023-10-14" @default.
• W2343122424 title "Do gene signatures predict effectiveness of bevacizumab and cetuximab?" @default.
• W2343122424 doi "https://doi.org/10.1200/jco.2008.26.15_suppl.14519" @default.
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