Apoptosis-based evaluation of chemosensitivity in cancer patients

Abstract

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.

1 - 11 . (canceled) 
   
   
       12 . A method for predicting a clinical response of an epithelial tumor or cancer to immunotherapeutic agents in a patient comprising:
 (a) culturing malignant epithelial cells having an unknown drug sensitivity profile from a patient tumor, ascites fluid, or pelvic washing;   (b) contacting the malignant cells with said agents separately in vitro; and   (c) detecting the level of caspase-3 activity induced by each agent, wherein induction of caspase-3 activity in vitro is indicative of sensitivity of the tumor or cancer cells in vivo, thereby predicting a clinical response to said immunotherapeutic agents.   
   
   
       13 . The method of claim  1 , wherein said tumor or cancer cells are epithelial ovarian cancer cells. 
   
   
       14 . The method of claim  1 , wherein said tumor or cancer cells are cultured to about 50-70% confluency before said contacting. 
   
   
       15 . The method of claim  1 , wherein said sample is contacted with said agents for about 4 hours to about 48 hours. 
   
   
       16 . The method of claim  1 , wherein caspase-3 activity is detected over a range of drug doses. 
   
   
       17 . The method of claim  1 , wherein caspase-3 activity is detected over time.