Gene Therapy Could Thwart Prostate Cancer Tumor-suppression Mutations, Study Reports

Gene Therapy Could Thwart Prostate Cancer Tumor-suppression Mutations, Study Reports
Prostate cancer patients who have mutations in the tumor suppressor gene PTEN could benefit from therapies targeting the CHD1 gene, according to a study. The research, “Synthetic Essentiality Of Chromatin Remodeling Factor CHD1 In PTEN-deficient Cancer,” was published in the journal Nature. Mutations in the PTEN gene, which prevents the expression, or activation, of cancer-associated genes, are often associated with prostate cancer. It is estimated that up to 70 percent of primary prostate tumors have PTEN gene mutations. To explore vulnerabilities in cancers with PTEN mutations, researchers focused on what is known as synthetic essentiality. This occurs when the simultaneous loss of two seemingly unrelated proteins leads to cell death, while mutations in either protein alone do not. The team identified the CDH1 gene as a possible synthetic-essential gene in PTEN-deficient cancer cells. Normally, PTEN promotes CHD1 degradation. If PTEN is absent, then CHD1 expression is stabilized, activating a signaling pathway that leads to cancer development. "We searched for genes that are occasionally deleted in some cancers but which are retained in cancers caused by specific tumor suppressing genes, such as PTEN," Di Zhao, PhD, and the study’s first author, said in a news release. "We reasoned that this retained synthetic essential gene might be required for cancer-promoting actions when the cancers lose specific tumor suppressor genes." The study showed that in PTEN-deficient prostate and breast ca
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