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

Julie L. Eiseman, Jianxia Guo, Ramesk K Ramanathan, Chandra P. Belani, David B. Solit, Howard I. Scher, S. Percy Ivy, Eleanor G. Zuhowski, Merrill J. Egorin

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2121-2127
Number of pages7
JournalClinical Cancer Research
Volume13
Issue number7
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

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tanespimycin
Insulin-Like Growth Factor Binding Protein 2
Biomarkers
Neoplasms
Therapeutics
Healthy Volunteers
docetaxel
HSP90 Heat-Shock Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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. / Eiseman, Julie L.; Guo, Jianxia; Ramanathan, Ramesk K; Belani, Chandra P.; Solit, David B.; Scher, Howard I.; Ivy, S. Percy; Zuhowski, Eleanor G.; Egorin, Merrill J.

In: Clinical Cancer Research, Vol. 13, No. 7, 01.04.2007, p. 2121-2127.

Research output: Contribution to journalArticle

Eiseman, Julie L. ; Guo, Jianxia ; Ramanathan, Ramesk K ; Belani, Chandra P. ; Solit, David B. ; Scher, Howard I. ; Ivy, S. Percy ; Zuhowski, Eleanor G. ; Egorin, Merrill J. / 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. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 7. pp. 2121-2127.
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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.",
author = "Eiseman, {Julie L.} and Jianxia Guo and Ramanathan, {Ramesk K} and Belani, {Chandra P.} and Solit, {David B.} and Scher, {Howard I.} and Ivy, {S. Percy} and Zuhowski, {Eleanor G.} and Egorin, {Merrill J.}",
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T1 - 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

AU - Eiseman, Julie L.

AU - Guo, Jianxia

AU - Ramanathan, Ramesk K

AU - Belani, Chandra P.

AU - Solit, David B.

AU - Scher, Howard I.

AU - Ivy, S. Percy

AU - Zuhowski, Eleanor G.

AU - Egorin, Merrill J.

PY - 2007/4/1

Y1 - 2007/4/1

N2 - 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.

AB - 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.

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