LASP-05: Time Course Assessment of Tumor Response to Therapeutics in Kras/p53 Pancreatic Ductal Adenocarcinoma (PDAC) Mice

The Laboratory Animal Sciences Program will breed 25 KPC animals with the intent of generating a cohort of 20 animals with confirmed tumor-load matching the following enrollment criteria: female mice are considered eligible for enrollment when ultrasound examination within 24 hours reveals 1 or 2 tumors, with the largest size being 6–11 mm and a combined tumor volume of 100–350 mm3. Animals with three or more tumors per organ; cystic tumors; signs of intestinal, pancreatic, or gall bladder duct occlusions; or otherwise moribund/showing signs of dilapidation will not be included in the study. One set of five animals for each of the four treatment arms will be collected at four weeks after treatment onset, and necropsies will be performed to collect blood and tissues of interest, (pancreas with tumor[s] and attached portion of gastrointestinal tract, liver, lungs, skeletal muscle, and brain). Pathology evaluation will be performed and slides prepared for histochemical evaluation of up to five biomarkers selected from the following set: proliferation markers (Ki67/ClC3, pERK, pAKT, and pMEK), stromal component/desmoplasia (Mason’s trichrome and collagen), immune infiltrates (CD3, CD4/CD8, B220, F4/80, and FoxP3), oxidative stress markers (Cox2, CA9. HIF1a, and ROS), and epithelial-to-mesenchimal markers (vimentin and E-cadherin). The exact set of biomarkers will be determined prior to the initiation of this study. The Laboratory Animal Sciences Program will assess disease outcomes for all collection groups and prepare a summary report. Alternatively, samples will be provided to the requestor for such assessment according to requestor’s specifications. Plasma and tissues will be provided for further endpoint evaluation.  

This service will take about five months to complete, and the Laboratory Animal Sciences Program will provide collected cryopreserved tissues and blood plasma, as well as a full study evaluation report. Sufficient basic consultation with a subject matter expert is included with the service.

Group

Treatment

Dose/Schedule

Collection at

n

1

Vehicle

TBD* IP, q4d x 8

4 weeks, X* hrs post-treatment

2

SoC(gemcitabine)

100mg/kg IP; q3d

4 weeks, X* hrs post-treatment

3

AS1

TBD* IP, q4d x 8

4 weeks, X* hrs post-treatment

4

AS2

TBD* IP, q4d x 8

4 weeks, X* hrs post-treatment

 
TBD* - Dosing concentrations will be provided by the requestor prior to the study beginning.
 

LASP-09: Assessment of Tumor Response to Therapeutics in Kras/p53 Non-Small Cell Lung Cancer Mice

The Laboratory Animal Sciences Program will induce a cohort of 30 KrasG12D;p53fl/fl mice by intratracheal instillation of AdenoCre recombinase to generate 20 KrasG12D;p53-/- mice for a short-term response to treatment study. Post-induction (after eight to nine weeks) all mice will be pre-screened by MRI for the presence of tumors and to randomize mice into treatment groups by tumor size. Twenty mice (five per group) will be treated with vehicle, chemotherapy, and two dose levels of the requestor’s compound (AE1) daily and necropsied after one week of treatment for blood and tissue collection. All mice will receive a post-treatment MRI scan prior to necropsy. Based on the requestor’s guidance, mice will be necropsied at a specified number of hours post-last treatment after the final dose. The Laboratory Animal Sciences Program will conduct a full pathology evaluation and histologic analysis will be conducted for four biomarkers.

The estimated time to dosing is 12 months. The Laboratory Animal Sciences Program will provide collected cryopreserved tissues and blood plasma, as well as study full evaluation report. Sufficient basic consultation with a subject matter expert is included with the service.

Group

Treatment

Dose; Schedule

Harvest

1

Vehicle

TBD PO, 3 wks on, 1 wk off

1 week, X hrs post-treatment

5

2

(Carboplatin)

25mg/kg IP; qd x 5

1 week, X hrs post-treatment

5

3

AE1 (Dose A)

TBD PO, 3 wks on, 1 wk off

1 week, X hrs post-treatment

5

4

AE1 (Dose B)

TBD PO, 3 wks on, 1 wk off

1 week, X hrs post-treatment

5

TBD* - Dosing concentrations will be provided prior to initiation of study by the requestor. Dose schedule: PO, QD, 1 week.