Nature Biotechnology pp 62 - 69

Researchers in Canada and the United States have developed a new screening approach for determining whether drugs act on targets that trigger desirable pathways in cells and can thus serve as more successful starting points for drug discovery. In the January 2004 issue of Nature Biotechnology, Charles Boone and colleagues describe an approach for elucidating potential mechanisms of action of chemical compounds. The strategy consists of exposing a collection of yeast strains, each with a single gene disrupted, to a compound of interest and then analyzing its effect on survival of the yeast. The authors then look for similar effects in strains in which an additional gene has been disrupted. By integrating the information gathered from the two screens, the authors are able to pinpoint specific genes and pathways affected by such compounds as cyclosporin A, an immunosuppressant drug, or caffeine. This information can be used to weed out candidate drug compounds in early testing stages by identifying undesired effects on pathways other than the targeted ones.

Hundreds of compounds are screened every day by pharmaceutical companies for their curative potential in assays on cells. Lead compounds subsequently undergo thorough analysis and testing to determine their mechanism of action and side effects. But in the vast majority of cases, the precise mechanism of action is never revealed and thus the potential of some drugs never fully realized. The new screening approach should help simplify the identification of new drugs and minimize the risk that they act on targets with deleterious effects.

Nature Biotechnology pp 93 - 97

Scientists have developed an improved method for performing sentinel lymph node biopsy, a crucial first step in determining whether a cancer has spread to other parts of the body. The new method, reported in the January 2004 issue of Nature Biotechnology, relies on tiny fluorescent crystals known as "quantum dots" to detect sentinel lymph nodes.

The body's lymphatic system drains fluid and cells to lymph nodes that contain cancer-fighting white blood cells. If cells have migrated from the initial tumor to the lymph node, it is a warning that cancer is spreading in the body. A sentinel lymph node is the first lymph node to receive drainage from a cancer-containing tissue. Compared with traditional surgeries, sentinel lymph node biopsy reduces surgical trauma for the patient and gives more reliable results by limiting the biopsy to a single lymph node. An important breakthrough in surgical oncology, it is being applied to an increasing number of solid tumors.

Using current biopsy methods, however, it is difficult for surgeons to detect sentinel lymph nodes, and first incisions have to be made essentially blindly by very experienced surgeons. John V. Frangioni, Moungi G. Bawendi and colleagues have shown that, by labeling sentinel lymph nodes with quantum dots, surgeons can see the nodes through at least one centimeter of tissue and accurately guide the surgery. The new method is also useful for ensuring that resection of the sentinel lymph node is complete.