A recent study employing CRISPR, a cutting-edge gene editing technology, has provided scientists with enhanced insights into the metastatic behavior of prostate cancer.
A recent study utilizing CRISPR, a state-of-the-art tool that enables gene modification, has offered researchers at Weill Cornell Medicine and their collaborators a clearer understanding of the spread, or metastasis, of prostate cancer.
Published on September 23 in Cancer Discovery, the research team mapped the complex pathways that metastatic prostate cancer cells navigate throughout the body.
“By creating virtual maps, we can uncover the concealed routes of metastasis, potentially leading us to innovative treatments that could block cancer’s progression,” stated Dr. Dawid Nowak, the study’s lead author and an assistant professor of pharmacology in medicine at Weill Cornell Medicine.
The Effects of Prostate Cancer Metastasis
Roughly 12% of men will be diagnosed with prostate cancer at some point in their lives. The American Cancer Society estimates that in 2024, approximately 35,250 deaths in the U.S. will be attributed to the disease.
“When prostate cancer spreads to the lungs, liver, and bones, it significantly impacts survival rates,” explained Dr. Ryan Serio, the study’s principal investigator and a postdoctoral fellow at Weill Cornell Medicine. Survival chances are nearly 100% when the cancer remains localized. However, once metastasis occurs, the survival rate plummets to under 40%.
Comprehending prostate cancer metastasis may lead to improved treatment options, according to Dr. Nowak, who is also an assistant professor within the Tri-Institutional PhD Program in Computational Biology and Medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.
A Novel Research Model
The research group established a new mouse model named EvoCaP to investigate prostate cancer’s progression and dissemination. In addition to Drs. Nowak and Serio, the team included Dr. Christopher Barbieri, an associate professor of urology at Weill Cornell Medicine, along with computational biologists Drs. Adam Siepel and Armin Scheben from Cold Spring Harbor Laboratory.
The researchers injected 12-week-old mice with a virus crafted to deliver genetic information to the prostate. This virus was designed to eliminate two tumor suppressor genes, promoting the growth and spread of prostate cancer, and to insert a “barcode”, a distinctive genetic marker that could subsequently be modified using CRISPR technology.
Utilizing additional tools like genetic sequencing and bioluminescence imaging, this barcode enabled the tracking of prostate cancer clones—cells derived from the primary cancerous cell that retain identical genetic mutations, proliferate, and metastasize. They monitored these clones as the mice aged up to 60 weeks.
“Through barcoding, we could follow clonal cells as they migrated to various metastatic locations in the body,” Dr. Serio remarked. The scientists identified the specific clonal cells that facilitated cancer spread and recognized the patterns of their dissemination. Notably, while the original tumor consisted of numerous prostate cancer cells, the majority of metastases originated from a small group of aggressive clones that moved from the tumor to the bones, liver, lungs, and lymph nodes.
They also discovered that once most cancer cells relocated to an organ, they tended to remain there rather than spread further, with only a few related cells triggering additional metastasis. “These spreading patterns, known as seeding topologies, in mice correspond to what has been seen in human cases“, explained Dr. Serio.
“We found it fascinating that the pathways of metastasis from our models corresponded to some extent with human cancer seeding patterns,” Dr. Nowak noted. “Using our methods to trace the paths of metastatic cells provides us a significant starting point for understanding how this lethal cancer propagates.”
Many physicians and researchers at Weill Cornell Medicine maintain collaborations with external organizations to encourage scientific progress and offer expert insight. This institution publicly shares these relationships for transparency. For more information, see the profile of Dr. Dawid Nowak.
This study was partially funded by the National Cancer Institute and the National Institute of General Medical Sciences, which are part of the National Institutes of Health, via grant numbers R01CA272466 and R35GM127070.
