DNA programme leads to breakthrough in prostate cancer metastases research | Wilbert Zwart at NU.nl

Metastatic prostate cancer cells that spread throughout the patient's body reactivate a DNA program responsible for fetal prostatic development, new research shows. Cancer researchers led by Wilbert Zwart of the Netherlands Cancer Institute and Oncode Institute, and Matthew Freedman of the Harvard Dana-Farber Cancer Institute in Boston, demonstrated this process in tissue samples taken from hundreds of surgically removed prostate tumors.

"Now we have a better understanding of how these metastases develop, we are one step closer to being able to prevent this life-threatening cancer stage”, according to cancer researcher prof. Dr. Wilbert de Zwart.

What did you discover?

“We discovered that once prostate cancer metastasizes, the tumor cell travels back in time to the embryonic state, when the prostate develops in utero. During fetal development, the formation of the prostate is facilitated by several activated DNA programs in specific locations."

"It’s like a manual. DNA in the embryo tells the cells how they should develop. Once the prostate is "done", these programs are turned off. And they remain off, even in patients with prostate tumors. Until the tumor metastasizes.”

What happens next?

“The metastatic cells seem to retain a memory of its previous activity. The tumor "abuses" this slumbering memory when spreading throughout the body. This turned out to be the case in every metastasis we studied. Quite a discovery.”

Why is this such a great discovery?

"Because no one has even been able to show that metastatic tumor cells reactivated DNA that has been inactive since fetal development, in order to metastasize. And all metastases seem to have reactivated this same program. This opens the door for all sorts of exciting follow-up questions.”

What kinds of questions?

"Now we know that prostate metastases use this embryonic program in the DNA, can we potentially prevent this? Can we deactivate this program? We are running experiments in our lab to find out. 

“And another question: is this process unique to prostate cancer, or do other tumor types also use this embryogenesis-specific program to metastasize? This is another thing we want to research.”

What does this discovery mean for future patients?

"We hope that this knowledge can translate to new treatment options that can prevent or slow down metastases. We hope that our research can help increase the survival rates for people with prostate cancer.”

“3000 out of all 13000 men who are diagnosed with prostate cancer every year end up dying of the disease. In nearly all of those cases, metastases are the cause. Metastases can turn cancer into a terminal disease. Now we know more about the ways in which tumors spread, we are another step closer to its prevention.”

This research has been made possible financially by the Dutch Cancer Society and Alpe d'HuZes ans is a collaboration between prof. dr. Wilbert Zwart of the Netherlands Cancer Institute and Oncode Institute and dr. Matthew Freedman of the Harvard Dana-Farber Cancer Institute in Boston. It has been previously published in Nature Genetics.

Bron: Nu.nl