New Gene Identification May Lead to Precision Therapy for Aggressive Prostate Cancer


Researchers are now reporting that the loss of a key gene (WAVE1) appears to be linked to a lethal form of prostate cancer.

Researchers are now reporting that the loss of a key gene (WAVE1) appears to be linked to a lethal form of prostate cancer.

Researchers at Upstate Medical University and Harvard University used bioinformatic meta-analysis to compare several publicly available databases, and they found that alterations in the WAVE1 (Wiscott-Aldrich Syndrome protein/WASP-family verprolin-homologous protein) gene were associated with a shorter period of remission in patients who were treated for prostate cancer. The findings were especially notable because they also showed that 22.9% of the prostate cancers reviewed in the database harbored the WAVE1 gene deletion.

Study co-author Leszek Kotula, MD, PhD, who is an associate professor of urology, biochemistry, and molecular biology at Upstate Medical University, Syracuse, NY, said the WAVE1 gene deletion occurs in metastatic and lethal cancer, suggesting that the WAVE1 gene loss may represent an aggressive subtype of prostate cancer which is more challenging to treat and more likely to progress. Dr. Kotula said it is possible that patients who have tumors characterized by the deletion of the WAVE1 gene may benefit from earlier intervention such as surgery, radiation therapy, and/or other therapies.

WAVE gene complexes are involved in cell motility and migration, cellular adhesion, and cell-to-cell communication. For these reasons, WAVE gene complexes can play a significant role in tumor progression and metastasis. Study investigator Adam Sowalsky, PhD, who is an instructor in medicine at Harvard Medical School in Boston, said the disruption of the WAVE complex is associated with human cancers, including prostate cancer. The research team has determined that because lethal prostate cancers show this disruption, it may be possible to identify mechanisms that lead to the tumor cell acquiring resistance to advanced therapies. However, Sowalsky said understanding the biological consequences of this deletion will require further investigation.

The study, which was published in the March 31, 2015 issue of Oncotarget, builds on earlier research by Kotula that implicated another gene, ABI1, as a tumor suppressor in prostate cancer. In this current study, researchers sought to find other genes that cooperate with ABI1 in the progression of prostate cancer.

Kotula said his lab is now replicating the WAVE1 gene deletion in mice. This project may lead to the development of drugs or new treatments to suppress tumors, or provide more precision in the treatment of these aggressive cancers. Prostate cancer is the most common form of cancer in men and is responsible for 27,000 deaths annually. About 220,000 new cases of prostate cancer are diagnosed each year.



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