Human cancer studied in unique mouse model

In an experiment reminiscent of Greek mythology, Ramzi Mohammad, PhD, has established a unique mouse model which allows for the growth of human pancreatic tumor cells within the body of a mouse. This unique SCID (severe combined immunodeficient) mouse has been established lacking an immune system and therefore allows human cells to grow unmolested. With this model, Dr. Mohammad has shown that human tumor cells can be safely injected directly into the mouse’s pancreas and can then be successfully treated. This is particularly groundbreaking for researchers to study how human tumors, orthotopically growing in their sites of origin, respond to particular treatments.

"The trouble with animal models is that you have to deduce what differences will exist in the human disease model," said Dr. Mohammad, who is an associate professor of internal medicine (hematology/oncology division) and researcher at the Barbara Ann Karmanos Cancer Institute. "This model is unique because it preserves the cellular structure of a human pancreatic tumor even though it exists within an animal model."

More important than the establishment of this model, however, is the potential treatment that could result from it. Dr. Mohammad has found a drug combination which is highly effective against pancreatic cancer--one of the most incurable and least understood of all human cancers. It is the fourth leading cause of cancer-related mortality and there has been no curative drug until now.

Gemcitibine is currently one of the most effective chemotherapy drugs available for pancreatic cancer. However, as Dr. Mohammad says, "Too many people are still dying. We have to find something better." So he began investigating auristatin-PE, which helps fight cancer by cutting off the blood vessels that carry nutrients to the tumor as well as arresting the tumor cells in their growth. Wayne State researchers have taken the lead on researching auristatin-PE, in fact, they’ve already produced six publications, reviewing its effectiveness against several cancers.

Dr. Mohammad and his colleagues published a study this year in Clinical Cancer Research, showing the success rates of various chemotherapy combinations, including the newly discovered auristatin-PE, against pancreatic cancer. "We had a 28.6 percent success rate with the gemcitibine-auristatin combination," said Dr. Mohammad. "In two out of seven mice, the cancer was completely cured. The tumors were eliminated and the pancreas was restored to its normal size--and because this treatment was tested on completely human tumors, the results are even more powerful. The drug didn’t cure animal cancer, it cured human cancer--so there’s no question in our minds."

Based on these preliminary results, Dr. Mohammad hopes that auristatin-PE will soon be considered for clinical trials. Furthermore, the results have drawn such a great response that the National Cancer Institute has asked Wayne State researchers to continue their investigations and look for curative potential in several other diseases too.