Dana-Farber, Broad Institute spot CYCLOPS gene class in cancer fight

Heard of CYCLOPS genes yet? You probably haven't, because the Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard just found and named them. Researchers believe that they may be potent new targets for cancer drugs because of their location--often next to tumor suppressor genes that are a struggle to effectively target.

Details are in the Aug. 17 issue of the journal Cell.

The researchers essentially tested a nearly 20-year-old theory by Dr. Emil Frei III, Dana-Farber's director and physician-in-chief from 1972 to 1991. When cancer strikes, chromosomes are thrown into turmoil and essential genes can be lost. Cancer cells, for example, can lose at least one of two copies of nearby tumor suppressor genes. And when tumor suppressor genes are lost, other neighboring genes that aren't involved in cancer development can also be lost. Frei's theory, published in 1993, was that if you block the copies left of those neighboring genes, you stop the cancer cells from growing and dividing because the few that remain are crucial to the cancer's survival.

The researchers' mission: to find cancer cells missing one copy of a gene that left the remaining copy vital to the cancer cell. Out of more than 5,312 genes in their initial pool, they found 56 that fit the bill and named them CYCLOPS genes (Copy number alterations Yielding Cancer Liabilities Owing to Partial losS). They also wanted to see how many of these genes were neighbors of missing tumor suppressor genes and many were, meeting Frei's hypothesis. Cancer cells turned out to be particularly dependent on one of the CYCLOPS genes in particular--PSMC2. In mice that had tumors lacking a copy of the PSMC2 gene, a PSMC2 blocking agent shrank their tumors.

In other words, the study authors believe that CYCLOPS genes are good targets for anti-tumor drugs because they are frequently near tumor suppressor genes. In cancers that have missing copies of tumor suppressor genes, hitting the nearby CYCLOPS genes, they say, could help to stop tumors from spreading.

All of this is incredibly early-stage, and years from human testing. But the identification of new drug targets warrants further testing, and CYCLOPS genes certainly showed promise, giving legs to an idea born nearly 20 years ago.

- read the release

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