Genes and Prostate Cancer

2012 Annual Report

Targeting the genetic drivers of lethal prostate cancers

Dr. Peter Nelson

Dr. Peter Nelson has discovered genetic mutations in aggressive prostate cancers, providing clues to why some prostate cancers are lethal and become resistant to treatment. This could lead to individualized treatments targeting the genetic drivers of these cancers.

Nearly all men will develop prostate cancer—if they live long enough. Yet its progression remains difficult to predict. In some men, the disease lies dormant for many years; in others, tumors rage in spite of treatment, spreading to the bones, where a cure is exceedingly rare.

Identifying new, more precise ways to individualize care for the disease’s varied forms is one of the major challenges confronted by the Hutchinson Center’s Dr. Peter Nelson, one of the nation’s leading prostate cancer researchers.

This year, Nelson and colleagues at the Hutchinson Center and University of Washington discovered three types of aggressive prostate tumors that mutate at a much faster rate than others and become resistant to treatment.

The discovery of these genetic mutations provides clues to why some prostate cancers are lethal, and potentially could lead to prevention methods, screening tests for early cancer detection or drug targets to slow or halt cancer growth, Nelson said.

The scientists found these “hypermutated” cancers after mapping the genomes of 23 lethal and drug-resistant forms of the disease, which until now had been poorly defined.

“The most interesting finding was the discovery of the three aggressive tumor types, which had 10 times the number of mutations compared to the other advanced prostate cancers we studied,” Nelson said. “That was very surprising and unusual. We don’t know the cause of these hypermutated tumors, but the frequency of the mutations suggests these tumors evolve very rapidly to develop resistance to therapies.”

The genetic knowledge of these lethal cancers could enable researchers to tailor treatments that target the genetic drivers of the cancers.

Nelson likens the aggressive tumors to Ferrari racecars. “If we can identify the molecular engines that drive the cancers, we may be able to block the fuel that runs those engines, which could slow or stop the cancer from progressing,” he said.

Nelson is hopeful this line of research could be one of the first successful steps to treat aggressive prostate cancer through precision medicine.

The next goals are to expand this research to other cancers and to help define its use in determining which patients to treat and which to watch closely. These are the types of big ideas Nelson and his research team are undertaking.

Dr. Peter Nelson’s discoveries on lethal prostate cancers were fueled by gifts from the Thomas C. Wright Foundation, the Richard M. Lucas Foundation and the Prostate Cancer Foundation.