GRN163L: Drug Candidate Against Lung Adenocarcinoma

Filed in archive Drugs, Vaccines and Therapeutics on September 5, 2005

Image: http://radiology.uchc.edu

Lung adenocarcinoma accounts for about 40 percent of lung cancers. By the time it is detected and treatment begins, the disease have already metastasised, or spread, to other areas. This is why mortality rate due to this particular form of lung cancer is high.

In the september issue of Cancer Research, however, researchers from the UT Southwestern Medical Center reports of a compound, designated as GRN163L that blocks telomerase, an enzyme that is known to keep cells immortal and that is implicated in cancer metastasis.

How does it work?

When normal cells divide and age, that part of the cell's chromosomes called the telomeres become shorter and shorter with each division. When they reach a certain length, the cells stop dividing. In cancer cells, however, the telomeres do not get shorter, because enzymes called telomerases bind to the telomere and prevent it from getting shorter, thus enabling cancer cells to keep on dividing indefinitely.

GRN163L contains a 13 nucleotide stretch that exactly matches the DNA sequence at the telomere. It competes with telomerases for binding positions, and given at the appropriate dose, may prevent telomerases from binding, eventually preventing metastatic tumors from forming.

Does it work? Yes, in mice. The researchers injected human lung tumor cells into the tails of mice and found that GRN163L blocked the development of metastatic tumors over several months. The higher the dose, the fewer tumors there were.

GRN163L has been recently approved by the US FDA for clinical trials.

The work was supported in part by the National Cancer Institute, Geron Corp.., Tubitak and the Turkey Education Foundation in Turkey.