Photo by Rhoda Baer
Researchers have established a public repository of leukemia and lymphoma xenografts, according to a report in Cancer Cell.
The repository, known as the Public Repository of Xenografts (PRoXe), contains material from bone marrow, peripheral blood, and lymph nodes of mice.
It also contains information on the patients from whom the cancer tissues were derived and details on the characteristics of the tumors themselves.
PRoXe is based at Dana-Farber Cancer Institute in Boston, Massachusetts, but it has a web portal that can be accessed by researchers around the world.
Those who register with PRoxE can access the repository and search for cells from patients with specific hematologic malignancies.
Researchers can then have frozen cells shipped to them and transplant the cells into mice to create patient-derived xenograft (PDX) models for testing drugs.
“About 90% of compounds that show anticancer activity in preclinical tests don’t work when given to patients,” said David Weinstock, MD, of the Dana-Farber Cancer Institute.
“By trying drugs in PDX models, we can ‘mimic’ large and expensive human clinical trials and get answers about efficacy more quickly, less expensively, and without the need for patients to get investigational drugs that won’t work.”
To demonstrate how PRoXe can be used, Dr Weinstock and his colleagues tested the MDM2 inhibitor CGM097 against B-cell acute lymphoblastic leukemia (B-ALL) in 2 groups of mice. One group had a mutation in the TP53 tumor suppressor gene, and the other did not.
The researchers observed superior survival in the mice with wild-type TP53. This result corresponds with the results of previous research, which showed that inhibitors that disrupt the MDM2-p53 interaction can be effective in tumor models and patient tumors with wild-type TP53.
Dr Weinstock and his colleagues said their results provide strong preclinical evidence for testing CGM097 in patients who have been extensively treated for B-ALL and have wild-type TP53.
Dr Weinstock also noted that the leaders of ProXe are negotiating with a number of academic centers in an attempt to incorporate their PDX models into the repository.
The Cancer Cell manuscript had 95 authors from 14 different centers that contributed samples, models, and/or effort to the project.
