Brookings, S.D. (KELO AM) - After apparently successful surgery, chemotherapy and radiation, there are still questions that haunt cancer survivors:When will the cancer come back as metastasis in other parts of my body? How will I know when it comes back? Will I respond to that therapy? Research now underway in the oncology field may provide answers to those questions in the not-too-distant future.
One of the researchers leading the way is Saraswati Sukumar (Sara-swatee SUK'-a-mar), an oncology professor at Johns Hopkins School of Medicine in Baltimore and co-director of the breast cancer program there.Sukumar will give two lectures in Brookings April 28, one to the general public and one to South Dakota State University College of Pharmacy faculty and students. Both lectures are open to anyone who is interested.
Her talk to the general public, "Using Personalized Molecular Profiles for Development of Blood Tests for Breast Cancer" is 7 p.m. in the downstairs theater of the South Dakota Art Museum. Sukumar, who holds a doctorate from Nagpur University in India, and was trained at the National Cancer Institutes in Bethesda, Md., has been conducting breast cancer research since before the turn of the century.
Studies have looked at what it is about the molecular properties of breast cancer cells that are different from normal cells, so as to develop treatments that target the cancer cells exclusively. She also has conceived of, and pioneered research that may deliver cancer treatment directly into the breasts' glands and ducts where the tumors appear, through openings in the nipple. This could deliver drugs directly to the tumor and bypass all side effects to the rest of the body.
Another goal of her work is to develop a blood test that detects very small amounts of DNA shed by the cancer into the circulation. This test can be an early indication of the metastatic return of cancer in survivors.
Successive tests proving 'amazing'Sukumar said there is "enormous" potential in this field and early studies have been encouraging. The first question is: how often does the test work to detect disease in those with metastatic breast cancer? The researchers have conducted blood tests in nearly 100 women with metastatic breast cancer and in normal women, and showed that they were able to detect it with higher than 90 percent accuracy.
The next phase of their testing, which has been recently completed in a field test of 140 patients, is in blood received from multiple institutions, and the researchers were blinded to the source of blood. Again, results from early data analysis are very promising, Sukumar said.In addition to detection of metastatic breast cancer, "we would like to use our test to find out if they are responding to treatment or not," Sukumar said.
"Imaging scans are done once every three or four months during treatment to assess response. Our preliminary tests show that the blood test may be able to assess responses in 15 days. "This is so much better than putting the patient through a three- or four-month round of chemotherapy, and then finding out that the tumors are not any smaller. Perhaps tests like this will help the doctor change the course of treatment, and administer better drugs sooner.
"She is amazed at the performance of the test. Why do I say it is amazing?" For the next best test, the accuracy rate is 30 to 40 percent," Sukumar said. Taking the test to the public happens in many small steps. After the field test wraps up this spring, the next stage is a national prospective trial. If successful there, the test has hopes of going commercial, she said.Finding 'needle in haystack'While Sukumar knew that blood would be the easiest material to work with in molecular testing for cancer cells, that doesn't mean that developing the test was easy.
"There are close to 10,000 genes that are methylated (expressed). Each tumor may have different genes that are expressed. So we needed to find a panel of genes that are commonly methylated in most breast cancers. We compared DNA from normal people and those with metastatic breast cancer."We came up with a panel of 10 genes that are very commonly methylated," Sukumar said.
Tumor cells shed enough DNA into the serum to be detected, but the number of copies shed is minute when compared to the millions and millions of copies of DNA shed by normal cells. "It is a virtual "needle in the haystack" story. We struggled with this problem for a while. We had to develop a method to be able to pick up these rare copies of DNA," she said.
"Then we had to do the careful analysis of sera from breast cancer patients and a like number from normal sera to evaluate how good the test was to detect tumor DNA specifically in sera of cancer patients," Sukumar said.
The development of the test and the marker panel took nearly five years and this process still might be refined as a result of the new trials being conducted, she said.In addition to her own research work, Sukumar will offer a "lay of the land on what other research work is being done towards the same goal both in Johns Hopkins and outside," she said.Separate session for facultyHer address to the scientific community is 2-3 p.m. April 28 in the Lewis & Clark Room (262) of the University Student Union. That message is
"Treating Breast Cancer by Targeting Cancer-Specific Metabolomic Alterations."There she will describe advances in research that aim to attack the changes in metabolism that cancer cells adopt in order to grow and divide. Again these changes in metabolism offer opportunities to cut off the supply of nutrients essential for the cancer cells to remain alive. Unlike normal cells that depend on glucose as a source of energy, breast cancer cells use amino acids as an energy source. Drugs like aminooxyacetate block the entry of amino acids into the energy producing metabolic processes, and thereby cut off the cancer cells source of energy, leading to their death. Also during Sukumar's two-day stay in Brookings, she will have individual meetings with pharmacy faculty members and have breakfast with graduate students and postdoctoral fellows.
The faculty will talk with Sukumar about starting a collaborative research project on developing a topical delivery method for breast cancer treatment.Sukumar's talk is the second annual Francis Miller Lecture in the College of Pharmacy, which is funded by a gift from the estate of Francis John "Johnny" Miller, a longtime pharmacist and drugstore owner in his hometown of Gettysburg as well as Redfield and Huron.For more information on the public lecture, call the college at 605-688-6197 or email sdsu.pharmacy@sdstate.edu.