BETHESDA, Maryland—New findings by proteomics researchers at the National Cancer Institute (NCI) and the Food and Drug Administration (FDA) have advanced efforts to enable physicians to monitor the response of cancer patients treated with molecularly targeted drugs and to diagnose ovarian cancer in the early stages of the disease.
The NCI released the outcomes of three studies originally intended for presentation at the 94th Annual Meeting of the American Association for Cancer Research (AACR) in Toronto. [The 2003 AACR meeting was canceled because of concerns about the threat of severe acute respiratory syndrome (SARS) in Toronto and has now been rescheduled for July 11-14 in Washington, DC.]
In a study led by NCI’s Virginia Espina, MS, MT, researchers identified several proteins—particularly one called AKT—that may prove useful in monitoring the progress of women treated for breast and ovarian cancer (abstract 2963). The approach involves measuring changes in the levels of active proteins inside tumor cells as a means of determining early in treatment whether a drug is working.
Molecularly targeted drugs are aimed at specific molecules in cancer cells, which allows monitoring of the signaling pathways the drugs are likely to affect. NCI researchers currently have studies underway to monitor the key pathways influenced by imatinib(Drug information on imatinib) (Gleevec), trastuzumab(Drug information on trastuzumab) (Herceptin), and gefitinib(Drug information on gefitinib) (Iressa).
Ms. Espina and her colleagues isolated breast cancer cells from tumor biopsies, measured protein levels in the signaling pathways targeted by trastuzumab, and determined how much of each protein was active. They measured the proteins before and several times after the women received trastuzumab therapy.
Prior to treatment, patients with poor outcomes tended to have higher levels of AKT, which promotes cell survival, than the women with better outcomes. Trastuzumab resulted in a decrease in active AKT, which may have enabled cell death, presumably by apoptosis. "Treatment with Herceptin appears to alter the level of active AKT in tumors," said senior investigator Lance Liotta, MD, PhD, of NCI. "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."
The researchers also suggested that the protein caspase 2, part of the molecular cascade that results in apoptosis, might be a key marker of whether a cell will follow the pathway to survival or death.
