Antitumor effects and biomarkers of activity of AZD0530, a Src inhibitor, in pancreatic cancer

N. V. Rajeshkumar, Aik Choon Tan, Elizabeth De Oliveira, Chris Womack, Helen Wombwell, Shethah Morgan, Madhuri V. Warren, Jill Walker, Tim P. Green, Antonio Jimeno, Wells A. Messersmith, Manuel Hidalgo

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Purpose: To determine the efficacy of AZD0530, an orally active small molecule Src inhibitor, in human pancreatic cancer xenografts and to seek biomarkers predictive of activity. Experimental Design: Sixteen patient-derived pancreatic cancer xenografts from the Panc-XenoBank collection at Johns Hopkins were treated with AZD0530 (50 mg/kg/day, p.o.) for 28 days. Baseline gene expression profiles of differently expressed genes in 16 tumors by Affymetrix U133 Plus 2.0 gene array were used to predict AZD0530 sensitivity in an independent group of eight tumors using the K-Top Scoring Pairs (K-TSP) method. Results: Three patient tumors of 16 were found to be sensitive to AZD0530, defined as tumor growth <50% comparedwith control tumors (100%). Western blot and/or immunohistochemistry results showed that AZD0530 administration resulted in the down-regulation of Src, FAK, p-FAK, p-paxillin, p-STAT-3, and XIAP in sensitive tumor xenografts compared with control tumors. The K-TSP classifier identified one gene pair (LRRC19 and IGFBP2) from the 16 training cases based on a decision rule. The classifier achieved 100% and 83.3% of sensitivity and specificity in an independent test set that consists of eight xenograft cases. Conclusions: AZD0530 treatment significantly inhibits the tumor growth in a subset of human pancreatic tumor xenografts. One gene pair (LRRC19 and IGFBP2) identified by the K-TSP classifier has high predictive power for AZD0530 sensitivity, suggesting the potential for this gene pair as biomarker for pancreatic tumor sensitivity to AZD0530.

Original languageEnglish (US)
Pages (from-to)4138-4146
Number of pages9
JournalClinical Cancer Research
Issue number12
StatePublished - Jun 15 2009

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'Antitumor effects and biomarkers of activity of AZD0530, a Src inhibitor, in pancreatic cancer'. Together they form a unique fingerprint.

Cite this