TY - JOUR
T1 - Molecular basis of chemosensitivity of platinum pre-treated
ovarian cancer to chemotherapy
AU - Glaysher, S.
AU - Gabriel, F.
AU - Johnson, P.
AU - Polak, M.
AU - Knight, L.
AU - Parker, Katharine
AU - Poole, Matthew
AU - Narayanan, A.
AU - Cree, I.
N1 - Funders:
Applied Biosystems.
CanTech Ltd.
PY - 2010/8/24
Y1 - 2010/8/24
N2 - BACKGROUND:
Ovarian cancer shows considerable heterogeneity in its sensitivity to chemotherapy both clinically and in vitro. This study tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients’ tumours.
METHODS: The chemosensitivity of a series of 31 ovarian tumours, all previously treated with platinum-based chemotherapy, was assessed using the ATP-based tumour chemosensitivity assay (ATP-TCA) and correlated with resistance gene expression measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in a TaqMan Array following extraction of mRNA from formalin fixed paraffin-embedded tissue. The results were standardised against a housekeeping gene (PBGD), and assessed by multiple linear regression.
RESULTS: Predictive multiple linear regression models were derived for four single agents (cisplatin, gemcitabine, topotecan, and treosulfan), and for the combinations of cisplatin + gemcitabine and treosulfan + gemcitabine. Particularly strong correlations were obtained for
cisplatin, gemcitabine, topotecan, and treosulfan + gemcitabine. No individual gene expression showed direct correlation with activity in the ATP-TCA. Genes involved in DNA repair and apoptosis were strongly represented, with some drug pumps also involved.
CONCLUSION: The chemosensitivity of ovarian cancer to drugs is related to the expression of genes involved in sensitivity and resistance mechanisms.
AB - BACKGROUND:
Ovarian cancer shows considerable heterogeneity in its sensitivity to chemotherapy both clinically and in vitro. This study tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients’ tumours.
METHODS: The chemosensitivity of a series of 31 ovarian tumours, all previously treated with platinum-based chemotherapy, was assessed using the ATP-based tumour chemosensitivity assay (ATP-TCA) and correlated with resistance gene expression measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in a TaqMan Array following extraction of mRNA from formalin fixed paraffin-embedded tissue. The results were standardised against a housekeeping gene (PBGD), and assessed by multiple linear regression.
RESULTS: Predictive multiple linear regression models were derived for four single agents (cisplatin, gemcitabine, topotecan, and treosulfan), and for the combinations of cisplatin + gemcitabine and treosulfan + gemcitabine. Particularly strong correlations were obtained for
cisplatin, gemcitabine, topotecan, and treosulfan + gemcitabine. No individual gene expression showed direct correlation with activity in the ATP-TCA. Genes involved in DNA repair and apoptosis were strongly represented, with some drug pumps also involved.
CONCLUSION: The chemosensitivity of ovarian cancer to drugs is related to the expression of genes involved in sensitivity and resistance mechanisms.
U2 - 10.1038/sj.bjc.6605817
DO - 10.1038/sj.bjc.6605817
M3 - Article
SN - 0007-0920
VL - 103
SP - 656
EP - 662
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 5
ER -