Evaluation of plasma insulin-like growth factor binding protein 2 and Her-2 extracellular domain as biomarkers for 17-allylamino-17-demethoxygeldanamycin treatment of adult patients with advanced solid tumors Journal Article
| Authors: | Eiseman, J. L.; Guo, J.; Ramanathan, R. K.; Belani, C. P.; Solit, D. B.; Scher, H. I.; Ivy, S. P.; Zuhowski, E. G.; Egorin, M. J. |
| Article Title: | Evaluation of plasma insulin-like growth factor binding protein 2 and Her-2 extracellular domain as biomarkers for 17-allylamino-17-demethoxygeldanamycin treatment of adult patients with advanced solid tumors |
| Abstract: | Purpose: Interaction of 17-allylamino-17-demethoxygeldanamycin (17-AAG) with heat shock protein 90 results in proteasomal degradation of many proteins, including Her-2-neu, with subsequent decreased expression of insulin-like growth factor binding protein-2 (IGFBP-2). Concentrations of both IGFBP-2 and Her-2 extracellular domain (Her-2 ECD) in sera of mice bearing BT474 human breast cancer xenografts decrease after 17-AAG treatment. We investigated whether this phenomenon occurred in patients. Materials and Methods: Eight to 15 plasma samples were obtained between 0 and 72 h from 27 patients treated with single-agent 17-AAG at doses between 10 and 307 mg/m2 and 18 patients treated with 17-AAG at doses between 220 and 450 mg/m2 combined with 70 to 75 mg/m2 of docetaxel. Pretreatment plasma samples were also obtained from 12 healthy volunteers. Plasma IGFBP-2 and Her-2 ECD concentrations were quantitated by ELISA. Results: Pretreatment plasma IGFBP-2 concentrations in patients (171 ± 116 ng/mL) were 2-fold higher than those in healthy volunteers (85 ± 44 ng/mL; P < 0.05). Following 17-AAG treatment, there were no consistent dose-dependent or time-dependent changes in plasma IGFBP-2 and Her-2 ECD concentrations. IGFBP-2 concentrations decreased by ≥40% in 8 patients, increased 2- to 5-fold in 8 patients, and remained essentially unchanged in 29 patients. Her-2 ECD concentrations decreased by ≥40% in 10 patients, increased 1.5- to 5-fold in 2 patients, and remained essentially unchanged in 25 patients. Conclusions: As previously reported, IGFBP-2 concentrations in plasma of cancer patients are significantly higher than those in healthy volunteers. In contrast to a mouse model, 17-AAG treatment was not consistently associated with decreases in IGFBP-2 or Her-2 ECD concentrations in patient plasma. © 2007 American Association for Cancer Research. |
| Keywords: | clinical article; controlled study; protein expression; advanced cancer; dose response; solid tumor; antineoplastic agents; neoplasms; biological marker; animals; mice; breast cancer; protein degradation; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor 2; tumor markers, biological; drug effect; dose-response relationship, drug; enzyme linked immunosorbent assay; docetaxel; heat shock protein 90; receptor, erbb-2; insulin blood level; taxoids; benzoquinones; lactams, macrocyclic; 17 allylamino 17 demethoxygeldanamycin; somatomedin binding protein 2; insulin-like growth factor binding protein 2 |
| Journal Title: | Clinical Cancer Research |
| Volume: | 13 |
| Issue: | 7 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2007-04-01 |
| Start Page: | 2121 |
| End Page: | 2127 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-06-2286 |
| PUBMED: | 17404095 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 5" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus" |
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