The blog
Why Does Cancer Kill You?
Using Zebrafish to study highly metastatic melanoma cells
Richard White, M.D., Ph.D.
Memorial Sloan Kettering Cancer Center
I obtained an M.D. and a Ph.D., and am trained in both medical oncology and basic science research. My interest in cancer goes all the way back to medical school, when I was rotating at a small hospital in upstate New York and was completely amazed by what I saw: young people dying from metastatic cancer with essentially nothing real to offer them. By the time I began my oncology fellowship at the Dana Farber Cancer Institute in Boston several years later, I was sure that we must be improving, but I was wrong. On my first day of fellowship training, we were shown a graph of survival from metastatic cancer going back to the 1960s, and it was remarkable how little we had progressed. Patients, on average, were living a few months longer, but when you looked at the overall survival curves several years after diagnosis, we were doing amost next to nothing: most patients with metastasis were dead within 3 years.
After my clinical fellowship, I began to search for postdoctoral research positions, a "prelude" to starting my own research group in the future. And I was very clear about two things: 1) I wanted to study metastasis, and 2) I wanted to study it in a way radically different than what had been done over the past 50 years. It is for those reasons that I chose to do my postdcotoral training in Leonard Zon's lab at Children's Hospital Boston and the Harvard Medical School: he was starting to study cancer using zebrafish, a model very well known for its incredible genetic toolbox, ability to study drugs, and capacity for "seeing" what was happening due to imaging technologies.
The zebrafish, for me, seemed like the perfect way to study the question I was interested in: why does metastatic cancer kill you? Conceptually, there are two ways to go about the problem. First, you can make educated guesses about potential mechanisms, and then test each of those mechanisms to see if they kept the animal alive with their cancer. Second, you could simply study huge numbers of animals, identify the rare ones that are able to live with their cancer, and then figure out why that animal is able to do so. Both approaches are completely practical in the zebrafish, becasue I can study somewhere between 100,000 and 200,000 fish at a time. Statistically, my likelihood of finding a few that are completely tolerant of their tumor is very high, far higher than if I were trying to do this type of study in a mouse.
For all of these reasons, in my own lab at Memorial Sloan Kettering Cancer Center, I am studying how metastasis kills the zebrafish, and why some animals are completely tolerant of their cancer and do not die from it. This is with the expectation that what we find in the fish is broadly applicable to all species that die from cancer.
Thank you doctor White for thinking "out of the box"
Having the Casper fish gives a literal view of cancer progression
Love the video
https://consano.org/projects/why-does-cancer-kill-you/
Thought I'd share the primary thought from the national library of medicine
A quantitative system for studying metastasis using transparent zebrafish
"Abstract
Metastasis is the defining feature of advanced malignancy, yet remains challenging to study in laboratory environments. Here we describe a high-throughput zebrafish system for comprehensive, in vivo assessment of metastatic biology. First, we generated several stable cell lines from melanomas of transgenic mitfa-BRAFV600E;p53−/− fish. We then transplanted the melanoma cells into the transparent casper strain to enable highly quantitative measurement of the metastatic process at single cell resolution. Using computational image analysis of the resulting metastases, we generated a metastasis score, μ, that can be applied to quantitative comparison of metastatic capacity between experimental conditions. Furthermore, image analysis also provided estimates of the frequency of metastasis-initiating cells (~1/120,000 cells). Finally, we determined that the degree of pigmentation is a key feature defining cells with metastatic capability. The small size and rapid generation of progeny combined with superior imaging tools make zebrafish ideal for unbiased high-throughput investigations of cell-intrinsic or microenvironmental modifiers of +Corresponding Author: Richard White, M.D., Ph.D., Memorial Sloan Kettering Cancer Center, 1275 York Avenue, MB 424, New York, N.Y. 10065, Phone: 646-888-3415, whiter@mskcc.org. CONFLICT OF INTEREST DISCLOSURE:
Leonard Zon is a founder and Scientific Advisory Board member of FATE Therapeutics and Scholar Rock. He has stock in both companies.
HHS Public Access
Author manuscript
Cancer Res. Author manuscript; available in PMC 2016 October 15.
Published in final edited form as:
Cancer Res. 2015 October 15; 75(20): 4272–4282. doi:10.1158/0008-5472.CAN-14-3319."
https://www.ncbi.nlm.nih.gov/pmc/articl ... 715832.pdf