Cancer resistance from rewiring of genome’s regulatory network

Although life is supported by the intricate regulation of the many genes in the cell’s genome, Carl Zimmer’s 2010 article reported a recent study demonstrating that the astonishing ability of E-coli to tolerate radical rewiring of its genome’s regulatory network. Remarkably, the bacteria not only continue to feed and grow like they normally do, but also grow considerably better. The capacity of E-coli to tolerate substantial “rewiring” enables the bacteria to easily acquire resistance to survive stressful conditions, and may be the mechanism underlying Darwinian evolution.

In higher organisms, tolerance to this “rewiring” can be a leading cause to cancer. Cancer arises from chromosome instability resulting in the profound rewiring of the genome’s complex regulatory network. While this rewiring results in abnormal gene expression that drives uncontrolled cell division and migration, the rewiring is also crucial for tolerance/resistance of cancers to anti-cancer drugs. A recent 2010 article published in Cell (Sharma et al., 2010) showed that cancer cells could display reversible tolerance to drugs, due in part to their highly dynamic genomic regulatory network. Treatment destroys the majority of cells that make up the bulk of the tumor, but spares a small resistant cell population. The resistant population (also referred to as tumor initiating cells) initiates a recurrent tumor composed of not only resistant cells, but also non-resistant cells comparable to parental population. Thus similar to bacteria, it seems that cancer cells also use this conserved “rewiring” mechanism to resist anti-cancer drugs, and to drive cancer recurrence through natural selection.

More information can be found in:
Carl Zimmer’s article: http://www.wired.com/science/discoveries/commentary/dissection/2008/04/dissection_0418

Sharma et al., 2010: http://www.cell.com/fulltext/S0092-8674%2810%2900180-7#Summary


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