Scientists from Rockefeller University, New York have recently found a drug that could treat human prostate cancer cells by targeting a protein called PHLPP2, which may prevent cancer cells from spreading to other organs in the body.
The researchers, who embarked on a study, which was published in the Journal of Cell Biology, revealed that inhibiting PHLPP2 lowered the levels of MYC, an oncogenic protein that causes different types of cancer that cannot be targeted by conventional drug therapies.
According to David G. Nowak, assistant professor at Weill Cornell Medicine, MYC is a powerful oncogene because it drives cell growth and proliferation and enhances cell metabolism and survival. He explained further that it is estimated that 450,000 Americans are diagnosed each year with a cancer that is driven by MYC.
One type of cancer associated with elevated MYC levels is metastatic prostate cancer. According to the Pan African Med Journal, around 127 men in 100,000 will be diagnosed with prostate cancer during their lifetime. The disease is the second leading cause of cancer death among Nigerian men and is projected to kill over 30,000 people in 2019.
The vast majority of these deaths are the result of cancers that spread, or metastasize, from the prostate to other organs in the body.
A professor at Cold Spring Harbor Laboratory and Co-Senior Author of the new study, Lloyd C. Trotman, explained that five-year survival of metastatic prostate cancer is only 28 percent, whereas the five-year survival of prostate-confined disease is almost 99 percent.
The protein PHLPP2 is also elevated in metastatic prostate cancer cells. PHLPP2 is a phosphatase enzyme that can remove phosphate groups from other proteins, but the role of this protein in prostate cancer was previously unclear.
In the new study, Nowak, Trotman, and colleagues found that metastatic prostate cancer cells require PHLPP2 to survive and proliferate. They discovered that PHLPP2 helps stabilize MYC by removing a phosphate group that would otherwise trigger MYC’s destruction.
To comprehend the analogy, the researchers deleted the Phlpp2 gene in mice and found that doing so prevented prostate cancer cells from spreading to other organs. This is significant because researchers have been unable to develop treatments that directly inhibit MYC, as it does not contain any features that can be easily targeted with a drug.
Trotman and colleagues then turned to human prostate cancer cells, which they treated with a drug that inhibits PHLPP2. This lowered MYC levels and caused the cells to stop proliferating and died.
PHLPP2 does not appear to perform any essential functions in healthy cells, so researchers suggested the enzyme could be an attractive way to indirectly target MYC in metastatic prostate cancer and possibly other cancers, too.
“Our results suggest that targeted efforts to design pharmacologically relevant PHLPP2 inhibitors could result in very efficient new drugs that suppress MYC-driven cancer,” Trotman said.