Table 6.
Pioglitazone and metformin alter biomarkers downstream of PAK in human disease. Clinical trials, which utilized pio or met in diseases with PAK overexpression, were analyzed for their immunohistochemistry data. Biomarkers: apoptosis (BCL2, MUC1), cell cycle control (CyclinD1, Ki67, P21), PI3K/mTOR (PS6K1, PS6Ser235), and PPARγ. Symbols indicate (+) treatment or (-) not available. (up or down arrow; 0) indicates percent increase or decrease in expression analyzed via IHC. 0 (no change); 1 arrow (>1% change): 2 arrows (>10% change); 3 arrows (>20% change); 4 arrows (>50% change).
| Biomarker Analysis in Cancer Patients Treated with Pioglitazone or Metformin | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Disease | Drug | Marker analyzed via immunohistochemistry (IHC) | Study ID | ||||||||||
| Apoptosis | Cell cycle control | PI3K/mTOR | PPARy | ||||||||||
| pioglitazone | metformin | BCL2 | MUC1 | CyclinD1 | Ki67 | P21 | PS6K1 | PS6ser235 | Total | Nuclear | Cytoplasm | ||
| Oral leukoplakia | + | - | ↓ ↓ |
- | ↓ ↓ |
↓ | ↑ | - | - | - | ↓ ↓ ↓ |
↑ | NCT0095 1379 |
| Non-small cell lung Ca | + | - | - | 0 | ↓ ↓ ↓ ↓ |
↓ ↓ |
↓ | - | - | ↑ ↑ ↑ ↑ |
- | - | NCT0134 2770 |
| Prostate Ca | - | + | - | - | - | ↑ ↑ |
- | - | - | - | - | - | NCT0143 3913 |
| Esophageal Ca | - | + | - | - | - | - | - | ↑ | - | - | - | - | NCT0144 7927 |
| Colon Ca | - | + | - | - | - | - | - | - | 0 | - | - | - | NCT0131 2467 |