A new technique may allow physicians to monitor patients' responses to molecularly targeted drugs, according to researchers from the National Cancer Institute (NCI) and the Food and Drug Administration (FDA). The finding is one of the newest in the field of proteomics - the study of proteins within cells.

In their study, the researchers successfully identified specific proteins that may be useful in monitoring patients treated for breast or ovarian cancer. Their approach, based on changing levels of active proteins inside tumor cells, could help physicians determine early during treatment whether a particular drug is working effectively for an individual cancer patient.

"The results of our study suggest this approach may help us tailor treatment to individual patients," noted Virginia Espina, M.S., M.T. (ASCP), NCI, the lead investigator on the study.

Because molecularly targeted drugs are designed to target specific molecules that have gone awry in cancer cells, researchers can predict which of the cell's many complex signaling pathways these drugs are likely to affect. In ongoing studies at NCI, researchers are using proteomic technology to monitor the key pathways likely to be influenced by the molecularly targeted drugs Herceptin®, Gleevec® and Iressa®.

To monitor changes in tumor cell proteins, the researchers isolated cancer cells from tumor biopsies and measured the level of various proteins involved in the signaling pathways targeted by the drugs. The scientists measured not only the total amount of each protein, but also how much of the protein was in its active form. These proteins were measured prior to treatment and at selected times after treatment.

The researchers found that prior to treatment, patients with breast cancer who had a poor clinical outcome tended to have more of the active form of a protein known as AKT, which promotes cell survival. Treatment with Herceptin®, however, resulted in a change in the relative amount of the active form of AKT, enabling tumor cell death.

"Treatment with Herceptin® appears to alter the level of active AKT in tumors. We may be able to measure the degree of this change in patients who are receiving treatment to determine whether a drug that inhibits this signaling pathway is best for their individual cancer," said Lance Liotta, M.D., Ph.D., co-director of the Clinical Proteomics Program and the senior NCI investigator on the study.

The researchers expect to be able to apply the proteomic approach to monitor the treatment of other cancers with molecularly targeted drugs, but further research is required to identify the best proteins to measure in those tumors.

SOURCE:
National Cancer Institute (http://www.nci.nih.gov)