BRCA2-inherited prostate cancers are predisposed to turn treatment resistant.
BRCA2-inherited prostate cancer is naturally primed to turn aggressive, and is the reason why some men develop aggressive, localized cancers that are treatment resistant, according to a study published in Nature Communication.
In the study, the investigators compared 15 patients with BRCA2-inherited prostate cancer with 500 prostate cancer patients from the general population who have non-inherited prostate cancer.
In a related study published in Nature that examined 500 tumors from Canadian men with non-inherited prostate cancer, the analyses led to the discovery of a new genetic fingerprint that identifies when curable diseases may turn aggressive.
The investigators found that genes normally involved in regulating cell growth and division are abnormal in BRCA2-associated cancers right at the start and, therefore, are resistant to therapy, taking on an aggressive trajectory, according to the study.
“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,” said co-principal investigator Dr Robert Bristow. “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 [sic] 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. This might include different types of chemotherapy or the use of molecular-targeted drugs that specifically target the changes associated with BRCA2 mutation.”
Dr Bristow added, “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. It is an example of the power of international collaboration and team science to crack the genetic code even in the rarest of tumors.”