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 cancers, CHD1 was more active. When it was inhibited, there was “profoundly and specifically suppressed cell proliferation, cell survival and tumorigenic potential,” the research team wrote.

When researchers looked through prostate cancer genome databases in the Cancer Genome Atlas, they found that CHD1 appears to be consistently active in cases of PTEN-deficient prostate cancer.

The findings support the notion that synthetic-essential genes may be valuable therapeutic targets in cancers carrying tumor-suppressor deficiencies.

“Identifying targets essential to cell survival in tumor suppressor genes has long been an investigational goal, with the aim of offering cancer-specific vulnerabilities for targeted therapy,” said Ronald DePinho, MD, senior author of the study. “This study provided a conceptual framework for the discovery of ‘traceable’ targets in cancers harboring specific tumor suppressor deficiencies.”

Related --

Related --

Leave a Comment

Your email address will not be published. Required fields are marked *