Toward a Cure for Advanced Prostate Cancer

By

A powerful new animal model for metastatic prostate cancer known as RapidCaP reveals a cancer-gene 'switch' that drives metastasis. That is the finding of research done at Cold Spring Harbor Laboratory on Long Island in New York. The study was published on January 24^th 2014 in the journal Cancer Discovery.

A release from the laboratory notes that prostate cancer is the most common and the deadliest form of cancer in men. The disease affects about 1 in 6 men, yet until now research has been stymied by imperfect animal models that are costly, take considerable time to develop, and fail to mimic the most lethal aspects of the illness. The most widely used mouse models for prostate cancer rarely develop tumors that metastasize, making it almost impossible to study the terminal, lethal events in cancer progression.,Now the Cold Spring Harbor Laboratory scientists led by Associate Professor Lloyd Trotman have developed a new method that rapidly creates much better mouse models for metastatic prostate cancer. This discovery allows scientists to investigate the causes of the disease while at the same time testing new therapeutics to treat it.

To create the new model, RapidCaP, the scientists surgically deliver gene mutations directly into the prostate. The also inject as luminescent marker that enables live monitoring of metastasis, tumor regression after treatment, and disease relapse.

Trotman and his team, which included collaborators from Weill Cornell Medical College, Mt. Sinai School of Medicine and the Dana-Farber Cancer Institute, used RapidCaP to generate mice that developed metastatic prostate cancer with classic hallmarks of this disease, including resistance to hormone therapy. However, PI 3-kinase activity, a well-known driver of prostate cancer, was notably absent from the metastasized tumors. In these deadly dispersed tumors, Trotman and his colleagues were surprised to find that a different cancer gene, called Myc, had taken over.

The team explored Myc's role in metastasis. They found that prostate tumors could be driven to metastasize simply by increasing the amount of Myc protein. Trotman collaborated with Dana-Farber's Professor James Bradner to treat these very sick animals with a newly discovered drug called JQ1 that lowers the amount of Myc in cells. Their approach succeeded in shrinking the metastases, suggesting that the switch to Myc is required for maintenance of tumor cells that have metastasized throughout the body.

The release quotes Trotman as saying, "The RapidCaP system has revealed a specific role for Myc as a druggable driver of metastasis in prostate cancer. So there's hope that our model provides a fast and faithful test-bed for developing new approaches to cure the type of prostate cancer that today is incurable."