We still have a lot to learn about how prostate cancer actually spreads, or metastasizes. Current theory holds that the primary tumor is probably most responsible for the development of distant metastases.
In a new genomic analysis of tissue performed at the Johns Hopkins University using tissue from prostate cancer patients this paradigm has been called into question. The genomic evidence shows that cells from other than the primary metastases also migrate to other body parts and form new sites of spread on their own.
“The idea that metastatic tumors can seed and establish other metastatic tumors in patients is different from traditional theories that the primary tumor is solely responsible for disseminating cancer cells with metastatic potential,” says William Isaacs, Ph.D., the William Thomas Gerrard, Mario Anthony Duhon and Jennifer and John Chalsty Professor of Urology at the Johns Hopkins Brady Urological Institute and a member of The Johns Hopkins Kimmel Cancer Center. “The new genomic information lends more support to the idea that treatments for metastatic cancers should be a combination of therapies that target a variety of genetic pathways.”
The data described came from a report of the work online April 1 in Nature, were generated from a novel set of samples, collected in a Johns Hopkins autopsy program for patients with prostate cancer from 1995 through 2004.
The researchers used extensive genome sequencing and bioinformatics analysis of tumor samples. Scientists at the Wellcome Trust Sanger Institute, University of Tampere in Finland and members of the International Cancer Genome Consortium had already found that the genetic makeup of cells within metastatic prostate tumors matched the makeup of new tumors from other metastatic sites, supporting this premises.
The Johns Hopkins researchers used a catalog of the genetic code of 51 tumors removed from 10 men who died from prostate as well as a sample of normal tissue from each of them.
The significant finding of the whole-genome sequencing was that “even though a single cell begins the metastatic process, the disease becomes very heterogeneous as it spreads throughout the body over time, both between and among individuals. In individual patients, each metastatic site becomes an entity unto itself,” says Isaacs, who also is a professor of oncology at the Johns Hopkins University School of Medicine.
The scientists found that five of the 10 men had patterns of mutations across several metastatic lesions, suggesting that these lesions were derived from not one but multiple metastatic sites. In seven of the men, the metastatic tumors were genetically more similar to each other than to the primary tumor.
This study clearly validates the theory that the original tumor is not the only agent of proliferation. It also shows us that to successfully treat advanced prostate cancer we need to recognize its inherent heterogeneity, which means we need to stack the cancer on multiple fronts simultaneously.
Joel T. Nowak, M.A., M.S.W.