BETHESDA, MarylandNew 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 proteinsparticularly one called AKTthat 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 (Gleevec), trastuzumab (Herceptin), and
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
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.