January 01, 2017
De Marzo and Bieberich: Combining mutations in two genes set off the process of widespread metastasis.
Scientists can’t safely test possible new cures without an animal model, and not having a model for the very worst kind of prostate cancer has limited what they could do to help the men who need it most.
Now, thanks to recent work — a project that began with funding from the Patrick C. Walsh Prostate Cancer Research Fund — there is such a model: a new mouse, developed in the laboratory of developmental biologist Charles J. Bieberich Ph.D., from the University of Maryland Baltimore County in collaboration with De Marzo. The team, including Hopkins scientists Gretchen Hubbard, Ph.D. (formerly a graduate student with Bieberich), and Vasan Yegnasubramanian M.D. Ph.D., and Peter Nelson, M.D., from the University of Washington, found that they could set off the process of widespread metastasis in a mouse by combining mutations in two genes that are commonly changed in human prostate cancer, MYC and PTEN.
“Interestingly,” De Marzo notes, “alteration of either one of these genes alone led to the development of small, relatively indolent prostate cancers that did not progress over time.” But William B. Isaacs, Ph.D., has shown in previous work that when both of these genes are mutated in human prostate cancer tissues, there is “a very high chance for the cancer to be aggressive and to become fatal. Thus, there is a tight concordance between what we have learned in humans suggesting which genes might be important for aggressive disease, and the new mouse data showing that indeed, this is the case.” Because the new mouse has both genes altered, scientists who use this model can study metastasis in depth, and look at different strategies for stopping it at various stages as the cancer progresses.
The next step will be to focus on making the mouse model easier to use, “so it can be widely employed by many researchers for testing of promising new treatments.” Others involved in the study include Laura Mutton, May Khalili, Ryan McMullin, Jessica Hicks, Daniella Bianchi-Frias, Lucas Horn, Ibrahim Kulac, and Michael Moubarek.