Targeting Epigenetics and Metabolism to Prevent Cancer Growth

New research has helped to clear up the function of a well-known tumor suppressor gene, RB, which prevents aberrant cell growth. Tumor suppressor proteins stop cell proliferation in order to prevent the uncontrollable formation of malignant tumors. The most well-known tumor suppressor; RB is named after childhood retina cancer. The first tumor suppressor gene related to susceptibility for retinoblastoma was the very first “anti-oncogene,” or tumor suppressor gene, identified in humans. It was also the first anti-oncogene to be knocked out of mice, which then went on to develop tumors. pRb, the protein encoded by this gene, affects cell replication, growth, differentiation, interaction with other cells, and apoptosis.

This research focuses on an epigenetic aspect of pRb’s impact on cancer, specifically how it affects histone demethylase KDM5A. The scientists found that pRb prevents the growth of tumors by restricting KDM5A, a molecule that represses the function of the mitochondria, or the “powerhouses” of the cells, in providing energy to cells that are healthy. Cancer cells, on the other hand, are much more primitive in comparison to healthy cells, and instead, need only to ferment sugars to obtain energy. The activation of a significant amount of genes can be triggered by epigenetic histone modifications. Tumors tend to be more aggressive when the cancer cell is immature, or less differentiated. The team of scientists discovered that if mitochondrial oxidation was restored in pRb-deficient cells, then they matured and weren’t as likely to divide.

A challenge is to identify cancer-specific vulnerabilities in biological pathways that are frequently disrupted under the control of epigenetics. In addition, epigenomic changes also contribute to the ability of tumor cells to escape detection by the human immune system, a concept that cancer immunotherapy tries to leverage. The paper identified several layers of molecular communication where epigenetic regulators are involved in tumor metabolism and regulatory activity. Taken together, precision medicine in combination with cancer systems biology may have the ability to reveal genome and epigenome-wide alterations to identify molecular pathways suitable for drug targeting:

·         Epigenomic master regulators can cause cancer in two ways: too much epigenetic activation can trigger oncogenes; too much epigenetic safeguarding can block tumor suppressor genes. Eventually, both mechanisms promote and progressing cancer.

·         Epigenomic changes and metabolites, human cellular chemistry, are tightly linked and rely on each other. Metabolites initiate, target, or maintain epigenetics, and vice versa. In addition, there is a strong cooperation between epigenetic factors with the transcriptional complex. Cooperation with metabolites can target, amplify, or mute these coded responses.