Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer

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 con...

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Published inDisease markers Vol. 2016; no. 2016; pp. 1 - 7
Main Authors Stopeck, Alison T., Iannone, Maria, Livingston, Robert, Chalasani, Pavani, Marron, Marilyn, Brown-Glaberman, Ursa, Specht, Jennifer
Format Journal Article
LanguageEnglish
Published Cairo, Egypt Hindawi Publishing Corporation 01.01.2016
John Wiley & Sons, Inc
Subjects
Adult
Aged
Angiogenesis Inhibitors - therapeutic use
Anthracyclines
Antigens, Neoplasm - blood
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - enzymology
Cancer
Carbonic Anhydrase IX
Carbonic Anhydrases - blood
Chemotherapy
Cyclophosphamide - therapeutic use
Doxorubicin - therapeutic use
Enzyme-linked immunosorbent assay
Female
Health aspects
Humans
Indoles - therapeutic use
Metastasis
Middle Aged
Neoadjuvant Therapy
Neoplasm Metastasis
Paclitaxel - therapeutic use
Prognosis
Pyrroles - therapeutic use
Sunitinib
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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.
AbstractList 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.
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.
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.
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. 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. 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. 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.
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.INTRODUCTIONCarbonic 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.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.METHODSIn 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.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.RESULTSPlasma 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.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.CONCLUSIONSOur 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.
Audience Academic
Author Stopeck, Alison T.
Livingston, Robert
Marron, Marilyn
Chalasani, Pavani
Iannone, Maria
Brown-Glaberman, Ursa
Specht, Jennifer
AuthorAffiliation 4 Stony Brook Cancer Center, SUNY Stony Brook, Stony Brook, NY 11794, USA
3 Fred Hutchinson University of Washington Cancer Consortium, Seattle, WA 98019, USA
1 University of New Mexico Cancer Center, Albuquerque, NM 87131, USA
2 University of Arizona Cancer Center, Tucson, AZ 85719, USA
AuthorAffiliation_xml – name: 2 University of Arizona Cancer Center, Tucson, AZ 85719, USA
– name: 4 Stony Brook Cancer Center, SUNY Stony Brook, Stony Brook, NY 11794, USA
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– name: 1 University of New Mexico Cancer Center, Albuquerque, NM 87131, USA
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Snippet Introduction. Carbonic anhydrase IX (CAIX) is a hypoxia regulated metalloenzyme integral to maintaining cellular pH. Increased CAIX expression is associated...
Introduction . Carbonic anhydrase IX (CAIX) is a hypoxia regulated metalloenzyme integral to maintaining cellular pH. Increased CAIX expression is associated...
Carbonic anhydrase IX (CAIX) is a hypoxia regulated metalloenzyme integral to maintaining cellular pH. Increased CAIX expression is associated with poor...
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SubjectTerms Adult
Aged
Angiogenesis Inhibitors - therapeutic use
Anthracyclines
Antigens, Neoplasm - blood
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - enzymology
Cancer
Carbonic Anhydrase IX
Carbonic Anhydrases - blood
Chemotherapy
Cyclophosphamide - therapeutic use
Doxorubicin - therapeutic use
Enzyme-linked immunosorbent assay
Female
Health aspects
Humans
Indoles - therapeutic use
Metastasis
Middle Aged
Neoadjuvant Therapy
Neoplasm Metastasis
Paclitaxel - therapeutic use
Prognosis
Pyrroles - therapeutic use
Sunitinib
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Title Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer
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