Genetic mutation in prostate cancer linked to later aggressive cancer


A new study examined how a genetic mutation in untreated patients is linked to aggressive prostate cancer later in life. It was previously thought that the mutation only occurred in response to therapy.

The research highlights why relapses could occur in some men following hormone therapy for prostate cancer. Also, it could help with much earlier identification of those patients that will develop fatal prostate cancer so that they can receive life-extending therapy. The study was published in the British Journal of Cancer (2014; doi:10.1038/bjc.2014.13), and it was carried out by scientists at the University of East Anglia (UEA) in Norwich, United Kingdom, and at the Institute of Cancer Research, London.

Treatment options for patients diagnosed with early-stage prostate cancer vary from “watchful waiting” to hormone-withdrawal therapy, radiotherapy, or surgery. Additional tests for indicators of aggressive cancer are necessary to help categorize patients. Then, those with a low-risk of the disease spreading can avoid unnecessary treatment, and those diagnosed with a high-risk can be targeted for more aggressive first line therapy.

Hormone-withdrawal therapy often results in a dramatic remission. However, the disease invariably relapses with a resistant form of the cancer occurring. A third of these relapsed cases are due to an increase in copy number of a particular gene called an androgen receptor. The gene is on the X-chromosome, so men normally only have one copy. Prostate cancer thrives on male hormones, and it increases the number of copies of the androgen receptor gene to grow better and to resist therapy.

“By the age of 60 [years], the majority of men will have signs of prostate cancer. However, only a small proportion of men will die of the disease. The question is—which of these cancers are dangerous and which are not? Deciding which cancers are going to progress and kill the patient is key to effective patient treatment,” said colead researcher Jeremy Clark, PhD, of the UEA.

Clark explained that this research indicated that about one-third of prostate cancers have an early form of gene boosting, meaning they have boosted the number of androgen receptor genes in their DNA, even though they were never treated with hormone reduction therapy. These are the cancers that are likely to grow and kill the patient.

“This discovery can be used to identify these killer cancers in patients much earlier than is currently possible. Patients could then be selected for more aggressive therapy before the cancer has developed full immunity,” said Clark.

The research team looked at biomarkers from almost 600 patients prior to hormone-withdrawal therapy. But the method of identification used was labor-intensive and time-consuming. Next, the team needs to develop ways of identifying patients for early therapeutic intervention so these findings can be implemented in the clinic. The research team is currently looking at more rapid ways of identifying patients that will develop aggressive cancer.

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