Each of us have genes which serve to suppress tumor growth. These antioncogenes actively protect cells from apoptosis, or “cell death.” Two of these guardian genes, BRCA1 and BRCA2, are given to mutation. In fact, hundreds of different types of mutations in these genes have been identified. Many of these variations have no practical effect, but others can be harmful – and can be passed from father to son.
Canadian and Australian prostate cancer researchers have just identified one such mutation that may be causing men to develop aggressive localized prostate cancer tumors that resist treatment and become lethal for up to 50 percent of patients within five years.
What's happening is that the genes normally involved in regulating cell growth and division are abnormal in the BRCA2-associated cancers right from birth and therefore are resistant to any kind of early onset prostate cancer therapy. They are “pre-set to be aggressive.”
The scientists compared 15 patients with BRCA2-inherited prostate cancer with 500 prostate cancer patients from the general population with non-inherited, or "sporadic,” prostate cancer. The work has led to the discovery of a new genetic fingerprint that identifies when curable disease may turn aggressive.
"The pathways that we discovered to be abnormal in the localized BRCA2-associated cancers are usually only found in general population cancers when they become resistant to hormone therapy and spread through the body," says co-principal investigator Dr. Robert Bristow, clinician-scientist at Princess Margaret Cancer Center, University Health Network. "These include pathways related to the repair of DNA damage, cell division, the receptor for the male hormone testosterone and cell-to-cell signaling.
"We now know need to explore the use of novel therapies to offset the BRCA2-associated aggressiveness earlier on in the treatment of these men and improve survival in an otherwise lethal tumor," he says. "This might include different types of chemotherapy or the use of molecular-targeted drugs that specifically target the changes associated with BRCA2 mutation.
"This is an exciting time in prostate cancer research in which the genetics of individual men and their cancers are beginning to dictate precise and customized treatment," he adds. "It is an example of the power of international collaboration and team science to crack the genetic code even in the rarest of tumors."
The research has been published in Nature Communications.