Sunday, March 23, 2008

Epigenetics - An Individualized, Future Approach to Cancer Treatment

Epigenetics - An Individualized, Future Approach to Cancer Treatment by
Derek Gene Kroll


Trivial findings are immense in the scientific community, especially in the field of oncology. Much emphasis is aimed at building upon previous laboratory discoveries; let's use the treatment of cancer as a broad example.

As many of you know, it is now common to combine independently discovered chemotherapy treatments, with or without radiation and/or surgical intervention. The heart of cancer breakthroughs have stemmed from this methodical combination. In recent news, a new and stirring foundation for future therapeutic combinations has surfaced.

The discovery can be attributed to vigilant scrutiny of biological processes within the tumor cell. The review, in the March issue of the New England Journal of Medicine, focuses on a specialty known as epigenetics. Epigenetics is associated with inheritable disparity in gene expression while retaining the same base sequence of DNA.

This essentially allows the cells, while stably maintaining the same DNA sequence, to assume different characteristics. Epigenetics is most commonly associated with x-chromosome inactivation in females, gene silencing, and post-transcriptional modification of amino acids.
Tumor cells are identifiable by numerous intracellular processes. For relevance and simplicity, I will only briefly discuss DNA methylation. Epigenetic processes can be marked by this methylation, which is vital to proper cellular function.

Upon observing a metastatic tumor cell, one would find an increasing degree of hypomethylation as the tumor became more invasive. The actual comparison of DNA methylation (normal cells) and hypomethylation (tumor cells) was originally observed in 1983 during the research of colon cancer. Dr. Manel Esteller, who authored the more recent review, explained that the tumor cells were in a DNA methylation paradox depending on the location of the nucleic acid in question.

The varying locations of DNA methylation directly contribute to the disturbance of chromosomes, or mutations, and inactivation of tumor suppressor genes, hence the abnormal behavior of tumor cells. How can this be related to future treatment options though?
Methylation can actually predict one's response to therapeutic treatment via protein analyzation.

The targeted protein is MGMT, also known as O6-Methylguanine-DNA methyltransferase, which is known to be significant in DNA repair. Observing MGMT for its degree of methylation allows the scientist a unique look at their prognosis with respect to certain DNA damaging drugs. For example: if MGMT is found to be hypermethylated, one can deduce the benefit of introducing DNA damaging drugs because the tumor cell will not be able to repair the DNA, leading to its death.

In conclusion, epigenetic markers can provide great insight into the potential of certain chemotherapeutic treatments: stepping away from mere protocol steps and into more individualized medicine. After all, it is the building upon minute discoveries and postulated treatments that will lead to the next breakthrough in cancer treatment

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