Epigenetics claims are all the rage. In the fuzzy world of epidemiology and a shocking lack of understanding about p-values and statistical significance, a whole lot of papers can get published using data that have nothing to say. Epigenetics takes that to another level, with claims that what you eat today could impact the chances of your grandchild getting into Harvard, and more.
But since epigenetic code, a language that does not change the basic code of our DNA but chemically labels active or inactive genetic information, can emphasize or silence genes, if that is disrupted, it might switch on oncogenes (genes that in certain circumstances transform cells into tumor cells) or shut down tumor suppressors. Both events will transform cells into tumor cells and cause cancer.
Speculative? Sure, but worth considering.
A new paper indicates that complementary forces of writers and erasers keep each other in check. If one force overtakes, the system gets out of equilibrium. For the cells this means either unlimited growth, cancer, or death. Researchers argue that once we have a better understanding of epigenetic regulation, scientists can design drugs that counter-regulate these factors. Recent multiomics (in general be extra cautious about fields ending in "omics", like you should worry about medical treatment from someone whose title ends in "path") data has identified an epigenetic writer, the methyltransferase EZH2, to be hyperactivated in many cancers including melanomas and lymphomas with poor prognosis owing to immune evasion and repression of tumor suppressors., The paper also showed that an epigenetic eraser, a member of the jumonji histone lysine demethylase family, KDM3A, takes on an oncogenic role by activating a network of tumor promoting genes.
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 and identify molecular pathways suitable for drug targeting:
1) 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 progress cancer.
2) 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 of epigenetic factors with the transcriptional complex. Cooperation with metabolites can target, amplify, or mute these coded responses.