Genes Need Education Too! Epigenetic Treatments in Cancer

Cancer is a genetic disease at the cellular level. Accumulated DNA damage (mutations) in genes controlling cell multiplication and communication causes uncontrolled growth. Recent research has shown that, alongside genetic structure, epigenetic factors examining gene-environment relationships also influence cancer development.

In our earlier article on this subject, we discussed how epigenetic factors contribute to cancer. In this article, we will learn how to educate genes against cancer.

Epigenetic mechanisms do not change gene structure, but determine whether genes are active.

Think of all our genetic information as a book and each page as a gene. Taping over a page prevents reading without changing it. This is exactly how epigenetic mechanisms affect genes.

Common epigenetic mechanisms in cancer are DNA methylation and histone modifications.

1. DNA Methylation: Chemical groups called methyl groups are added to DNA. A methylated gene region remains inactive and cannot perform its function.
2. Histone Modifications: Histone modifications determine gene activity. DNA has a thread-like structure in cells. Histone proteins wrap DNA into a compact structure. Genes inside the coil cannot be read and remain inactive.

Research has observed that the most common cancer mutations occur in DNA methylation mechanisms. However, excess or insufficient methylation varies by gene type.

For example, methylation is very high in tumor suppressor genes in cancer cells. When these genes lose activity, cells begin multiplying uncontrollably. Conversely, genes promoting cell division show low methylation, making oncogenes (genes promoting abnormal growth) more active than normal.

The main aim of epigenetic cancer treatment is to block enzymes/molecules performing epigenetic mechanisms. Most approved epigenetic therapies are used in blood and lymph cancers (leukemias and lymphomas). FDA (United States Food and Drug Administration)-approved drugs developed for this purpose include:

1. Azacitidine: Approved in 2004. Blocks the activity of methylating enzymes. Myelodysplastic syndromesubtypes are treated with it.
2. Decitabine: Approved in 2006. Blocks methylating enzyme activity. Used to treat myelodysplastic syndrome.
3. Vorinostat: Approved in 2006. Targets enzymes/molecules performing histone modifications. Cutaneous T-cell lymphomais treated with it.
4. Romidepsin: Approved in 2009. Targets enzymes/molecules performing histone modifications. Used to treat cutaneous T-cell lymphoma.
5. Ruxolitinib: Approved in 2011. Targets the activity of proteins causing immune suppression and cell division. Myelofibrosis is treated with it.

Epigenetic therapies are also being developed for solid tumors, all cancers other than leukemias and lymphomas. The main problem is the inability to deliver epigenetic drugs effectively to solid tumors. Clinical trials combining these with other treatments continue. Another difficulty is incomplete understanding of epigenetic mechanisms. The Human Genome Project revealed all our genetic information, but because our epigenome, all epigenetic information, has not yet been analyzed, effective drugs cannot be developed. Nevertheless, epigenetic treatments offer great hope. Damage to genes is irreversible , but epigenetic mechanisms are reversible (for example, when weight is gained or lost). This opens the way to effective cancer treatments.