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Genomic signatures to guide the use of chemotherapeutics. Authors: Anil Potti et. al Presenter: Jong Cheol Jeong. Motivation. What will be happened if ineffective chemotherapy is used?. Increasing the probability of side effects. Decreasing the quality of life. Purpose.
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Authors: Anil Potti et. al
Presenter: Jong Cheol Jeong
Increasing the probability of side effects
Decreasing the quality of life
NCI-60: composed with 60 cell line and the sensitivity to 5084 compounds
Sensitivity: exposing each cell line to each compound for 48hours, assessing the growth inhibition by sulforhodamine B
The concentration of compound requiring 50% cytotoxicResults
Cell lines from NCI-60
Blue: lowest expression
Red : highest expression
Validation of docetaxel response prediction model
30 lung and ovarian cancer cell lines
29 lung cancer cell lines
Significant correlation between predicted probability of docetaxel sensitive and IC50
showing the capacity of the predictor
Individual chemosensitivity predictions
Statistically significant distinction between the responders and nonresponders
Breast cancer with 45 cell lines
Kaplan-Meier survival analysis
FAC adjuvant chemotherapy
PPV: Positive Predicted Value
NPV: Negative Predicted Value
Step1. Chemotherapy response predictors calculates the likelihood of sensitivity to the seven agents in a large collection of samples
Ex) breast, lung, and ovarian tumor
Step2. Clustering the samples according to patterns of predicted sensitivity to the various chemotherapeutics and plotted a heatmap
Respond to 5-FU are resistant to Adriamycin and Docetaxel:suggesting possibility of alternate treatments
Red: high probability of sensitivity of response
Blue: low probability of resistance
Someone who initially responds to a given agent is likely to eventually suffer a relapse; therefore the development of gene expression signatures that reflect the activation of several oncogenic pathways are needed
Step1: stratifying the NCI cell lines based on predicted docetaxel response
Step2: examining the patterns of pathway deregulation associated with docetaxel sensitivity or resistance
17 lung cancer cell lines
Red: high probability of sensitivity of response or activation
Blue: low probability of resistance or deregulation
Significant relationship between phosphatidylinositol 3-OH (PI3)-kinase pathway deregulation and docetaxel resistance.
- Giving an opportunity to use a PI3-kinase inhibitor in this group