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    David Halvorsen  

Identifying and Disrupting Mediators of ALT

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This project is part of the following research theme(s):
  • OncoSENS

Project Description

One of the main OncoSENS research objectives involves disrupting the process by which cells (especially cancer cells) lengthen their telomeres. This objective is chosen because telomeres are one of the known mediators of replicative senescence – the loss of the ability of a cell to divide and thereby replace itself. That is, when telomeres get short via many cycles of cell division, cells lose the ability to divide further, and senesce. Of course, cancer cells replicate very prolifically, and the way this is accomplished involves the preservation of the cancer cells’ telomeres. Thus, if cancer cells’ ability to preserve telomeres can be disrupted, a replication limit can be forced upon cancer cells, meaning they can only ever grow so long (or a tumor so big) before they stop dividing, eliminating the ability of these cells to take over the body and cause the kinds of problems they currently do.

There are two known mechanisms used by cells (including cancer cells) to lengthen their telomeres: (1) by expressing the enzyme telomerase, and (2) by a process called alternative lengthening of telomeres (or ALT). SENS Foundation has made an objective of developing methods to disrupt both of these processes, to ensure that all cancer cells have a limit placed on their ability to divide, greatly diminishing their potential harmfulness.

The current project at the SENSF Research Center, begun in February 2012, aims to identify targets to eliminate (2), ALT - the relatively obscure, telomerase-independent method by which some cancer cells lengthen their telomeres.

It is estimated that approximately 10% of all cancers use ALT to lengthen their telomeres. ALT is relatively less-well studied than telomerase-mediated telomere lengthening. Because of this, the current project has been initiated at the Research Center to identify mediators of ALT which may potentially be disrupted. Identifying these mediators, and disrupting them safely and effectively, would disable even telomerase-independent cancers from endlessly dividing and causing the kinds of terrible health effects they currently do via unregulated cell division.

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