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Chromosomal translocations point the way toward personalized cancer care
Date:8/13/2012

A broken chromosome is like an unmoored beansprout circling in search of attachment. If a cell tries to replicate itself with broken chromosomes, the cell will be killed and so it would very much like to find its lost end. Often, it finds a workable substitute: another nearby chromosome. When a broken chromosome attaches to another, or when chromosomes use a similar process to exchange genetic material, you've got a translocation genes end up fused to other genes, encoding a new protein they shouldn't. A recent University of Colorado Cancer Center review in the journal Frontiers of Medicine shows that you also frequently have the cause of cancer and in some cases its cure.

"The most famous example is the Philadelphia chromosome the translocation and fusion of genes BCR and ABL that causes chronic myeloid leukemia," says Jing Wang, MD, PhD, University of Colorado Cancer Center investigator and assistant professor of immunology at the CU School of Medicine, the review's author.

Other oncogenic translocations include the fusion of genes ALK and EML4 to create what's known as ALK+ non-small cell lung cancer.

The promise of recognizing these cancer-causing translocations is the potential to target cells with these genetic mutations. Find a therapy that seeks and destroys a specific translocation or cells that have learned to depend on a translocation for survival and/or growth, and you can kill cancer without killing surrounding, healthy cells. In a nutshell, that's the goal of targeted cancer therapy the current revolution underway in cancer research to selectively target cancer cells.

"Since their discovery, chromosomal translocations have made a critical impact on diagnosis, prognosis and treatment of cancers," Wang writes.

In CML, the revolutionary drug Gleevec targets the energy mechanism of cells with the Philadelphia chromosome; in ALK+ lung cancer, the drug crizotinib, developed largely at the CU Cancer
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Contact: Garth Sundem
garth.sundem@ucdenver.edu
University of Colorado Denver
Source:Eurekalert

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