Table 1.
Effects of single-agent DAC in the KrasLSL-G12D; p53LSL-R270H/+; Pdx1-cre; Brca1flex2/flex2 (KPC-Brca1) mouse model of PDAC.
| Treatment started (age in weeks) | Age at necropsy (weeks) | Treatment (number of mice)a | Clinical Efficacy | Pancreatic Tumor Histopathology |
|---|---|---|---|---|
| Untreated | 3 weeks (n=4) | Untreated | N/A | 4 of 4 animals had high grade PanIN lesions; 2 of 4 animals had micro-invasive cancers |
| Untreated | 8 weeks (n=6) | Untreated | N/A | 6 of 6 animals had one or more invasive cancers |
| 3 weeks | 8 weeks | PBS (n=3) | control | 3 of 3 animals had one or more invasive cancers |
| DAC (n=3) | Tumor size reduced by ~90% (PBS-treated tumors, average size= 12.5mm; DAC-treated tumors, average size= 1.3mm)b | 1 of 3 animals had a single invasive cancer | ||
| 3 weeks | 9 weeks | PBS (n=3) | control | 3 of 3 animals had one or more invasive cancers |
| DAC (n=4) | Tumor size reduced by ~75% (PBS-treated tumors, average size= 10.7mm; DAC-treated tumors, average size= 2.7mm)c | 2 of 4 animals had one invasive cancer per animal | ||
| 3 weeks | Survival study | PBS (n=19) vs. DAC (n=12) | DAC extends survival by 40.5days; PBS (87 days) vs. DAC (127.5 days); p-value <0.0001 (Log- rank test) | (see below) |
| 8 weeks | Survival study | PBS (n=19) vs. DAC (n=21) | DAC extends survival by 23 days; PBS (87 days) vs. DAC (110 days); p-value <0.0001 (Log- rank test) | Sarcomatoid change in malignant epithelial cells and loss of CAFs in tumors escaping from DAC |
a
The treated animals received 1μg of DAC per gram of body weight, or PBS vehicle control, by i.p. injection once per week.
b
Pancreas weight reduced by 75% compared to PBS-treated pancreata (PBS-treated pancreata, average weight=0.8 g; DAC-treated pancreata, average weight=0.2 g).
c
Pancreas weight reduced by 88% (PBS-treated pancreata, average weight=1.72 g; DAC-treated pancreata, average weight=0.21 g)