Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer

Ursa Brown-Glaberman, Marilyn Marron, Pavani Chalasani, Robert B Livingston, Maria E Iannone, Jennifer Specht, Alison T Stopeck

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Introduction. Carbonic anhydrase IX (CAIX) is a hypoxia regulated metalloenzyme integral to maintaining cellular pH. Increased CAIX expression is associated with poor prognosis in breast cancer. To explore CAIX as a biomarker for breast cancer therapies, we measured plasma CAIX levels in healthy control subjects and in breast cancer patients. Methods. In control subjects we evaluated plasma CAIX stability via commercially available ELISA. We then similarly quantified plasma CAIX levels in (1) locally advanced breast cancer (LABC) patients treated with neoadjuvant paclitaxel + sunitinib (T + S) followed by doxorubicin and cyclophosphamide (AC); (2) metastatic breast cancer (MBC) patients treated with systemic chemotherapy. Results. Plasma CAIX levels were stable at room temperature for at least 48 hours in control subjects. Mean baseline plasma CAIX levels were lower in controls compared to patients with LABC or MBC. In LABC, CAIX levels rose significantly in response to administration of antiangiogenic therapy (T + S) (p = 0.02) but not AC (p = 0.37). In patients with MBC treated without an antiangiogenic agent CAIX levels did not change with therapy. Conclusions. Our results suggest that CAIX may be an easily obtained, stable measure of tumor associated hypoxia as well as a useful pharmacodynamic biomarker for antiangiogenic therapy.

Original languageEnglish (US)
Article number9810383
JournalDisease Markers
Volume2016
DOIs
StatePublished - 2016

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Carbonic Anhydrases
Breast Neoplasms
Plasmas
Therapeutics
Biomarkers
Cyclophosphamide
Carbonic Anhydrase IX
Pharmacodynamics
Angiogenesis Inhibitors
Chemotherapy
Paclitaxel
Doxorubicin
Tumors
Healthy Volunteers
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Biochemistry, medical
  • Clinical Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer. / Brown-Glaberman, Ursa; Marron, Marilyn; Chalasani, Pavani; Livingston, Robert B; Iannone, Maria E; Specht, Jennifer; Stopeck, Alison T.

In: Disease Markers, Vol. 2016, 9810383, 2016.

Research output: Contribution to journalArticle

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AU - Chalasani, Pavani

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AU - Iannone, Maria E

AU - Specht, Jennifer

AU - Stopeck, Alison T

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N2 - Introduction. Carbonic anhydrase IX (CAIX) is a hypoxia regulated metalloenzyme integral to maintaining cellular pH. Increased CAIX expression is associated with poor prognosis in breast cancer. To explore CAIX as a biomarker for breast cancer therapies, we measured plasma CAIX levels in healthy control subjects and in breast cancer patients. Methods. In control subjects we evaluated plasma CAIX stability via commercially available ELISA. We then similarly quantified plasma CAIX levels in (1) locally advanced breast cancer (LABC) patients treated with neoadjuvant paclitaxel + sunitinib (T + S) followed by doxorubicin and cyclophosphamide (AC); (2) metastatic breast cancer (MBC) patients treated with systemic chemotherapy. Results. Plasma CAIX levels were stable at room temperature for at least 48 hours in control subjects. Mean baseline plasma CAIX levels were lower in controls compared to patients with LABC or MBC. In LABC, CAIX levels rose significantly in response to administration of antiangiogenic therapy (T + S) (p = 0.02) but not AC (p = 0.37). In patients with MBC treated without an antiangiogenic agent CAIX levels did not change with therapy. Conclusions. Our results suggest that CAIX may be an easily obtained, stable measure of tumor associated hypoxia as well as a useful pharmacodynamic biomarker for antiangiogenic therapy.

AB - Introduction. Carbonic anhydrase IX (CAIX) is a hypoxia regulated metalloenzyme integral to maintaining cellular pH. Increased CAIX expression is associated with poor prognosis in breast cancer. To explore CAIX as a biomarker for breast cancer therapies, we measured plasma CAIX levels in healthy control subjects and in breast cancer patients. Methods. In control subjects we evaluated plasma CAIX stability via commercially available ELISA. We then similarly quantified plasma CAIX levels in (1) locally advanced breast cancer (LABC) patients treated with neoadjuvant paclitaxel + sunitinib (T + S) followed by doxorubicin and cyclophosphamide (AC); (2) metastatic breast cancer (MBC) patients treated with systemic chemotherapy. Results. Plasma CAIX levels were stable at room temperature for at least 48 hours in control subjects. Mean baseline plasma CAIX levels were lower in controls compared to patients with LABC or MBC. In LABC, CAIX levels rose significantly in response to administration of antiangiogenic therapy (T + S) (p = 0.02) but not AC (p = 0.37). In patients with MBC treated without an antiangiogenic agent CAIX levels did not change with therapy. Conclusions. Our results suggest that CAIX may be an easily obtained, stable measure of tumor associated hypoxia as well as a useful pharmacodynamic biomarker for antiangiogenic therapy.

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