Apoptosis-based evaluation of chemosensitivity in cancer...

G - Physics – 01 – N

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G01N 1/30 (2006.01) G01N 33/48 (2006.01) G01N 33/574 (2006.01)

Patent

CA 2547213

Induction of apoptosis in target cells is a key mechanism by which chemotherapy induces cell killing. An in vitro system has been established for determining carboplatin and paclitaxel (Taxol) chemosensitivity of epithelial ovarian cancer cells, where measurements of caspase-3 activation are surrogate markers for activation of chemotherapy-induced programmed cell death. To validate the assay as a predictor of clinical chemotherapy-induced programmed cell death. To validate the assay as a predictor of clinical chemosensitivity in vitro apoptotic response were compared to the clinical response of the patients from whom the tumor cells were isolated. Caspase-3 activation in response to in vitro chemotherapy to both drugs was shown to have an 83 % positive predictive value and a 71 % negative predictive value. Markers of apoptosis such as caspase-3 activation can be quantitated and utilized to predict the clinical response to chemotherapy.

L'induction d'apoptose dans des cellules cibles est un mécanisme clé par lequel la chimiothérapie induit la mort cellulaire. Un système <i>in vitro</i> a été établi pour déterminer la chimiosensibilité au carboplatine et paclitaxel (Taxol) des cellules cancéreuses ovariennes épithéliales, des mesures d'activation de caspase-3 étant des marqueurs de substitution pour l'activation de la mort cellulaire programmée induite par chimiothérapie. Pour valider le dosage comme une indication de chimiosensibilité clinique, des réponses apoptiques <i>in vitro</i> ont été comparées à la réponse clinique des patients chez qui les cellules tumorales ont été isolées. L'activation de caspase-3 en réaction à la chimiothérapie <i>in vitro</i> des deux médicaments s'est avéré avoir une valeur prédictive positive de 83 % et une valeur prédictive négative de 71 %. Les marqueurs de l'apoptose tels que l'activation de caspase-3 peuvent être quantifiés et permettent de prédire la réponse clinique à la chimiothérapie.

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