Biomarkers That Predict Sensitivity to Heat Shock Protein 90 Inhibitors.
Clin Breast Cancer
; 16(4): 276-83, 2016 08.
Article
en En
| MEDLINE
| ID: mdl-26726007
ABSTRACT
INTRODUCTION:
Heat shock protein (HSP) 90, a viable target for cancer treatment, mediates the maturation and stabilization of client oncoproteins. HSP90 inhibitors (HSP90i) are potentially active in a variety of tumors, but therapeutic benefit is confirmed in only a small subset. We explored potential biomarkers across multiple studies of HSP90i in advanced solid tumors. PATIENTS ANDMETHODS:
Archived tumor specimens from patients treated with HSP90i in 7 different phase I/II trials at Memorial Sloan Kettering Cancer Center were identified. Tumor tissue was tested using immunohistochemistry; estrogen, progesterone, and androgen receptors ≥ 1% positive and < 1% negative; HSP90 and HSP70 0, 1 + negative, and 2+, 3 + positive; phosphatase and tensin homolog 0 negative, 1 reduced, and 2 positive; HER2 0, 1 + negative, 2 + equivocal, 3 + positive; and epidermal growth factor receptor 0 negative, and 1+, 2+, 3 + positive. The expression of the biomarker panel was correlated with clinical benefit (CB) (defined by overall response [ORR] or CB by the "8-week" scan) using Fisher exact test.RESULTS:
Adequate tissue was available for 51 of 158 patients (32%), including 10 different solid tumors. Of these, 71% (36 of 51) and 51% (26 of 51) patients met the criteria to assess CB by best ORR or by the "8-week scan" assessment, respectively. Breast was the most frequent tumor. The mean duration of HSP90i therapy was 55 days (range, 16-411 days). There were 16 responses (4 partial response; 12 stable disease); 13 of 16 responses strongly correlated with HER2-positive status (P = .001).CONCLUSION:
Our findings suggest HER2 as a sensitive client and perhaps the only effective biomarker for sensitivity to these HSP90i.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
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Receptor ErbB-2
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Proteínas HSP90 de Choque Térmico
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Proteínas HSP70 de Choque Térmico
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Antineoplásicos
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Clin Breast Cancer
Asunto de la revista:
NEOPLASIAS
Año:
2016
Tipo del documento:
Article