Nature Medicine | Spoonful of Medicine

Mutations that drive early-onset prostate cancer identified, pointing way to specific treatments

Prostate cancer affects an estimated one in every six males who live past the age of 70, making it the most common type of cancer among men worldwide. The majority of prostate cancer cases occur in men 65 years of age or older, but about 2% of cases occur in those under the age of 50—and these early tumors are particularly aggressive. Until now, scientists didn’t know whether the mechanisms that give rise to prostate cancer in the younger men were different from those in seniors.

New findings, published today in Cancer Cell, show that in young patients prostate cancer develops through a distinct mechanism driven by androgen hormones, such as testosterone. “This brings up the intriguing possibility to develop future screening tests for prostate cancer geared towards young men in which testosterone levels are particularly high,” says molecular biologist Jan Korbel of the European Molecular Biology Laboratory in Heidelberg, Germany.

In an effort to understand the genetic and biological basis of prostate cancer in young men, Korbel and his colleagues sequenced the entire genomes of tumor cells isolated from 11 early-onset prostate cancer patients and compared them to the genomes of tumor cells obtained from seven elderly-onset prostate cancer patients.

The study revealed that the androgen receptors that bind testosterone were much more active in the tumor samples from the younger individuals than the older ones. Further analysis linked this testosterone-driven activation to increased DNA rearrangements that cause cancer, and additional data from more than 10,000 patients confirmed this connection. What’s more, the researchers observed that in the cells from nine out of 11 early-onset patients, testosterone activated androgen receptors that triggered the gene TMPRSS2 to ultimately fuse the gene ERG, promoting cancer. In contrast, the genomic landscape of elderly patients revealed abnormalities that were not linked to the androgen receptors’  activity.

Levi Garraway, a medical oncologist at Harvard’s Dana-Farber Cancer Institute in Boston who was not involved in the current study, thinks that the new link between the genomic landscape of prostate cancer and androgen-driven biology is “encouraging because half of the drugs [approved by the US Food and Drug Administration] for prostate cancer are attacking the androgen axis.” This reinforces that early-onset prostate cancer patients should receive such androgen-targeting drugs as part of first-line treatment. It’s “more bang for the buck,” Garraway says.

“[The] next step in the field should be to first stratify treatments for early and late onset,” Korbel says. Further studies are needed to asses if such tailored screening can lead to greater success in the disease detection, but the observed DNA rearrangement mechanisms in early-onset patients can be a more general phenomena as studies have shown that such rearrangements also lead to chromosomal alternations in breast, ovarian and pancreatic cancers.

 Image: Shutterstock


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    Science Is Here said:

    Our hopes are on personalized medicine: in the future, patients will profit from this new information concerning the genomic landscapes but also from the recently published epigenetic landscapes.