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Advanced Prostate Cancer Genome

The Dana-Farber Cancer Institute reported by the Stand Up To Cancer-Prostate Cancer Foundation Dream Team published a new study in the journal, Cell. The findings target a potential new drug therapy for treating prostate cancer. It's the first study of the genomic composition of prostate cancer. This shows many patients have gene mutations that can be targeted with existing or potential drugs. The findings are based on an analysis of tumor samples from 150 men with metastatic prostate cancer. 

These men no longer responded to standard hormone blocking therapy. Many patients may carry some type of genetic abnormality that can be targeted with existing or potential drugs.

Eight institutions from the United States and Europe contributed tumor samples to the project. Evidence that genomics driving advanced prostate cancer is fundamentally different than primary prostate cancer. Knowing about these genomic differences means they can be treated differently in a clinical setting.

Advanced disease can be treated with different targeted therapies than primary PCa.

Previous studies have surveyed the genomic characteristics of tumors confined to the prostate gland. New study is the first to focus on metastatic hormone resistant prostate cancers. These are difficult to treat because they often develop resistance to standard treatment.

Found that almost all the tumors had at least one genetic abnormality known to drive cancers.

Most common, found in nearly two-thirds of the samples, were abnormalities in genes responsible for the androgen receptor.  Cell structure that sends growth signals in response to the male hormone androgen. Not surprising since the hallmark of castration-resistant disease is that it no longer responds to conventional androgen-blocking therapies.

  25% of patients had mutations in the DNA repair genes including BRCA1 or BRCA2 genes, which are known to increase the risk of breast and ovarian cancer. Drugs known as PARP inhibitors have already been approved for BRCA-positive ovarian cancer, suggesting that PARP inhibitors may prove effective in prostate cancers with this type of aberration.

8% of patients had an inherited genetic alteration. Genetic counseling may be appropriate for patients with prostate cancer. In the next phase of the study, researchers will genetically sequence tumor cells from at least 500 patients and follow the course of their disease. Will track how patients with specific genetic abnormalities respond to certain treatments, improving doctors' ability to treat the disease.