Prostate cancer usually grows so slowly that only about 1% of patients diagnosed with early-stage disease die from it over the next 15 years. But because physicians have no foolproof method to separate aggressive cancers from indolent ones, most patients opt for treatment, risking complications such as impotence and incontinence.
![Pathologists can diagnose prostate cancer, shown here, with a microscope, but they can't precisely determine how it will behave. [Photo from iStockphoto.]](https://aacr.silverchair-cdn.com/aacr/content_public/journal/cancerdiscovery/1/5/10.1158_2159-8290.cd-nb10311-23/8/m_368photo4.jpeg?Expires=1683128167&Signature=iJvzA0O9UrzxgfUikTSPIDlqVkWjTQuhVQ8KqK02JRF4xG37B7lZLJDL4l9PNxNxcIWIXxW9ffaiZNNlc9tnFXA3FpiG56ZDrLUWh6DHI9R7f-cFzDKy50RUHbaznGx9advRqVr5ff1CkxrPYg8P9BE295A6ryhU8xBaKmykHfGVqPTHqvVJnG0uE4onyvP9QAsDStmTUWc1NNk1dFRSY3ot2mwHG5IetptgRVDU1mZx8TDv2sVSSTZLQwslpmFrz5VEtKcSrR3p3kQBSq5jUqrKoLdofGF~mkNFJh3AUhbEPn5VMXK6VIi5eBxSsiy5J6~YU3SUCJ5FkZcLclfnQw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Pathologists can diagnose prostate cancer, shown here, with a microscope, but they can't precisely determine how it will behave. [Photo from iStockphoto.]
Pathologists can diagnose prostate cancer, shown here, with a microscope, but they can't precisely determine how it will behave. [Photo from iStockphoto.]
The discovery of a new prostate cancer tumor suppressor gene, PHLPP1, and studies examining its relationship to the tumor suppressor gene PTEN may simplify decision-making for newly diagnosed patients—and may point to the most effective drugs for recurrent cancers.
Studying mice, researchers at Cold Spring Harbor and other laboratories found that Phlpp1 keeps the oncoprotein Akt in check, much like Pten, which is mutated in roughly half of prostate cancer patients (Cancer Cell 2011;20:173–86). But in Pten-deficient animals lacking both copies of Phlpp1, Akt activity kicked into overdrive. Although the master tumor suppressor p53 delayed progression of the disease, tumors eventually overcame that too.
The researchers then examined more than 200 primary and metastatic tumor samples from men. Almost none of the primary cancers were missing both PTEN and PHLPP1, but both genes were frequently deleted in metastatic tumors, along with p53. By measuring expression levels of PTEN and PHLPP1 in biopsy or prostatectomy samples, doctors could determine the likelihood of an aggressive cancer and the chances of disease recurrence.
“Low RNA transcription activity for these genes seems to herald a future problem,” says Lloyd C. Trotman, PhD, the study's leader. “About 70% of these patients will have a recurrence within 10 years.”
Checking for mutations of PTEN, PHLPP1, and the closely related PHLPP2 in circulating tumor cells in relapsed patients could also help determine which ones would be candidates for clinical trials of drugs that inhibit the PI3-kinase/AKT pathway, when these patients should start taking the drugs (based on p53 status), and which drugs might be optimal for them.
