JAX® In Vivo Cancer Services
JAX® NOTES Issue 513, Spring 2009
Experienced technical staff
Program Director Neal Goodwin, Ph.D., is experienced in preclinical drug development. He served a postdoctoral fellowship in functional genomics at The Jackson Laboratory in the laboratory of Dr. John Schimenti, now at Cornell University. He served as a Senior Scientist in the Mouse Genetics/Genomics and Biotechnology program at Pharmacia, where his responsibilities included mouse modeling of multiple therapeutic areas including cancer. Neal most recently served as Chief Scientific Officer and Co-founder of ProNAi Therapeutics, where his responsibilities included the discovery/development of a new class of cancer therapeutics for multiple cancers.
Study Director Sandra Biroc, Ph.D., oversees xenograft, orthotopic and metastatic cancer models projects. Previously, as a researcher at Berlex Biosciences, she investigated the xenograft efficacy of novel targeted therapies in solid tumors, specializing in orthotopic and metastatic mouse models. As a researcher at Axys Pharmaceuticals, she investigated small molecule protease inhibitors in models of angiogenesis, osteoporosis, asthma and rheumatoid arthritis. As a founding member of Khepri Pharmaceuticals, Sandra developed assays for neutral endopeptidase and cysteine protease inhibitors for rheumatoid arthritis and cancer.
Xenograft and endogenous tumor models
The most widely used models for cancer and preclinical drug discovery are xenograft models, whereby human cell lines derived from human tumors are propagated and engrafted into immunocompromised mice. JAX offers dozens of these models for different cancers. They are especially useful for quickly estimating drug efficacy, preparing the way for Investigational New Drug (IND)-enabling safety studies, and, ultimately, for human trials.
JAX, the NCI-MMHCC, and others offer exquisitely engineered luciferase-expressing endogenous tumor models for use with biophotonic imaging technology.
Orothotopic prostate tumor response to docetaxel over a five-week study.
Biophotonic imaging: testing drug efficacy in vivo
Under an agreement with Caliper Life Sciences, JAX uses the IVIS® biophotonic imaging system to monitor drug response of surgically implanted luciferase-expressing tumor cells in a live mouse (no need for necropsy). The system is ideal for orthotopic studies in which human tumors are grown in orthologous mouse regions (prostate cancer in the prostate, breast cancer in the mammary fat pad, bone metastases in bone, colon cancer in the colon, etc.). Scientists at the new facility have already validated the use of this technology to study prostate and lung cancer.
This technology significantly accelerates drug development: In vivo efficacy studies can be initiated and executed efficiently, fewer mice are needed and tumor response can be estimated quite well from the light signal. The technology is also very well suited for imaging and tracking endogenous cancer models with luciferase-expressing tags.
Luciferase expression from orthotopic prostate tumor in an anesthetized NU/J (002019) mouse.
