Screening technique streamlines search for anticancer drugs

Most cancer patients face an all or nothing dilemma. Aggressive chemotherapy can and often does kill cancerous cells, shrink tumors and increase a patient's chance for survival. But chemo's toxic chemicals kill healthy cells too, causing severe side effects like anemia, organ damage and even memory loss.

In a study reported in the March 24 issue of Cancer Cell, researchers detail an approach to rapidly identify chemical compounds that are active only in the presence of certain cancer-causing genes and proteins--a step toward finding drugs that are lethal only to cancer cells. This strategy, which pairs chemical compounds with the specific genetic mutations they are likely to react against, also opens the door to a new way to custom-tailor chemotherapy.

Brent Stockwell and his colleagues at Whitehead Institute for Biomedical Research in Cambridge, Mass., used a novel screening technique to survey more than 23,000 chemical compounds and test for their ability to kill human cancer cells. In particular, Stockwell mined this "chemical library" for compounds that killed cancer cells while leaving healthy cells unharmed. The group identified nine compounds matching this profile, including one previously unidentified compound that seems to kill cancer cells through a different mechanism than many conventional cancer drugs.

High-throughput, Quick Results

Over the last decade, researchers have identified some of the genes and proteins most commonly implicated in the cascade of cellular events leading to cancer. In this study, Stockwell used human cancer cells engineered to contain a selection of these common genetic aberrations, including the ras and htert oncogenes and two known oncoproteins (proteins implicated in cancer development).

The lab developed a screening assay that exposed the engineered cancer cells to a barrage of chemical tests. Results of these tests were fed into a database that tracked the results and scored th

Contact: Melissa Withers
Whitehead Institute for Biomedical Research

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