Type

Journal Article

Authors

Norma O'Donovan
John Crown
Martin Clynes
Dimitrios Tryfonopoulos
Thamir Mahgoub
Anne-Marie Larkin
Susan Kennedy
Lorraine O'Driscoll
Alex J Eustace

Subjects

Medicine & Nursing

Topics
cav 1 dasatinib biomarkers anxa1 epha2 predictive biomarker cancer melanoma mrna expression protein expression clinical trials cell lines treatment

Predictive biomarkers for dasatinib treatment in melanoma (2014)

Abstract Dasatinib has anti-proliferative and anti-invasive effects in melanoma cell lines. However clinical trials have shown modest activity for dasatinib in metastatic melanoma. Although dasatinib targets SRC kinase, neither expression nor phosphorylation of SRC appears to predict response to dasatinib. Identification of predictive biomarkers for dasatinib may facilitate selection of melanoma patients who are more likely to respond to dasatinib. We correlated the anti-proliferative effects of dasatinib in 8 melanoma cell lines with expression of a previously identified 6-gene biomarker panel. We examined the relationship between response to dasatinib and expression of each gene at both the mRNA and protein level. Dasatinib inhibited growth in 3 of the 8 cell lines tested. mRNA expression of the panel of 6 biomarkers did not correlate with response, whilst elevated protein expression of ANXA1, CAV-1 and EphA2 correlated significantly with response to dasatinib in the panel of cell lines. Expression of ANXA1, CAV-1 and EphA2 were analysed in 124 melanoma samples by immunohistochemistry. ANXA1 protein was detected in 81 % (97/120) of tumours, CAV-1 in 44 % (54/122) of tumours and EphA2 in 74 % (90/121) of tumours. Thirty one % (35/113) of tumours tested expressed all three markers and 19 % (21/112) had moderate or strong expression of ANXA1, CAV-1 and EphA2. Seventeen percent (19/112) of melanoma samples were positive for SRC kinase expression, combined with high expression of ANXA1, CAV-1 and EphA2. This subgroup may represent a population of melanoma patients who would be more likely to derive clinical benefit from dasatinib treatment.
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Full list of authors on original publication

Norma O'Donovan, John Crown, Martin Clynes, Dimitrios Tryfonopoulos, Thamir Mahgoub, Anne-Marie Larkin, Susan Kennedy, Lorraine O'Driscoll, Alex J Eustace

Experts in our system

1
Norma O'Donovan
Dublin City University
Total Publications: 52
 
2
John Crown
Dublin City University
 
3
Martin Clynes
Dublin City University
Total Publications: 209
 
4
Thamir Mahgoub
Dublin City University
Total Publications: 6
 
5
Anne-Marie Larkin
Dublin City University
Total Publications: 6
 
6
Susan Kennedy
Dublin City University
Total Publications: 37
 
7
Lorraine O'Driscoll
Trinity College Dublin
Total Publications: 152
 
8
Alex J Eustace
Royal College of Surgeons in Ireland
Total Publications: 23