Gauging cancer cell vulnerability.

• Position: Cancer Treatment

The first potential treatment targeting a pathway by which several aggressive tumors maintain their ability to proliferate has been identified by researchers from the Massachusetts General Hospital Cancer Center and Boston University School of Medicine. Treatment with a small molecule that blocks a key step in that pathway--the alternative lengthening of telomeres (ALT) pathway--was able to inhibit the growth and survival of ALT-positive tumor cells.

"Identification of genetic markers that predict cancer cell vulnerabilities and new drugs to exploit such vulnerabilities is a focal point of cancer research today," says Lee Zou, associate scientific director of the MGH Cancer Center. "Cancer cells must rely on either the telomerase enzyme or the ALT pathway to bypass the normal processes of cell aging and death. Our findings may provide a new direction for the treatment of ALT-positive cancers--which include osteosarcoma, glioblastoma, and certain pancreatic tumors."

Telomeres are repetitive DNA sequences that sit at the ends of chromosomes and serve a protective function to make sure cells do not lose valuable genetic information each time they divide. When telomeres have been eroded to a critically short length, they send out a signal to the cell telling it to stop dividing, ensuring that the genetic information remains intact but limiting the cell's life span. Cancer cells have evolved to overcome this constant attrition by continuously extending those eroded telomeres, promoting cellular immortality.

There are two major pathways for telomere elongation in cancer cells. The more common pathway relies on the enzyme telomerase to extend telomeres. The less understood ALT pathway lengthens telomeres through recombination with DNA sequences from other chromosomes.

In their investigations, the researchers studied how the action and expression of several key...