Finding a Cure: Research Updates & Highlights
Fort Wayne, Indiana (June 2, 2008) — The Vera Bradley Foundation for Breast Cancer has pledged $10 million to accelerate breast cancer research at the Indiana University Melvin and Bren Simon Cancer Center. This pledge has resulted in the naming of the Vera Bradley Center for Breast Cancer Research Laboratories.
New laboratories for the 28-member breast cancer research team will open in 2009, but the research is ongoing and incredible progress is being made toward understanding and battling breast cancer.
Speaking of the accomplishments of this team George Sledge, M.D., co-leader of the Breast Cancer Program at the Indiana University Melvin and Bren Simon Cancer Center, says, “I’m honored and blessed to work with an astonishing group of laboratory and clinical researchers. Cancer research is collaborative research. The days where you had a lone genius working on breast cancer or any disease are over. This is an era where we need creative thoughts from many people in many different fields working together, and we’ve been able to foster that here at Indiana University.”
To that end, team members are focused on both understanding the biology underlying breast cancer, and applying that understanding to improve prevention, diagnosis and treatment.
Understanding the Biology Underlying Breast Cancer:
Linda Malkas, Ph.D., the Vera Bradley Chair in Oncology and co-director of the Vera Bradley Center for Breast Cancer Research Laboratories, and her colleague, Robert Hickey, Ph.D., have discovered a key protein present in breast cancer cells, raising hopes that this will lead to a significantly better method for early detection of the disease. This particular protein plays a vital role in the processes that control cell replication, cell repair and cell death. They have also identified an antibody that differentiates between the normal form of this protein and the altered form found in breast cancer cells, making it possible to detect cancer before a tumor ever forms. In addition, the duo has demonstrated the same key protein is present in ovarian cancer, resulting in the same promise for early detection of this hard-to-diagnose and aggressive cancer.
Brittney-Shea Herbert, Ph.D., studies telomeres, proteins at the end of chromosomes, and telomerase, enzymes that promote DNA transcription in telomeres. She is currently collaborating with Dr. Malkas on chromosome research. Many cancer cells are considered immortal because telomerase activity allows them to divide virtually forever, which is why they can form tumors. A very specific type of activity is present in 90% of all breast cancers and this same activity does not take place in normal cells. The hope is that studying the chromosomes’ structure will help lead to an early diagnosis of breast cancer, when it’s most treatable.
A normal, healthy breast tissue bank, co-directed by Anna Maria Storniolo, M.D., and Susan Clare, M.D., Ph.D., is now accessible to breast cancer researchers nationally. The bank is a 2,500-specimen bio-repository of tissue and bio-molecules donated by women, most of whom have never had breast cancer. The tissue samples—blood, spit, and actual breast biopsies—are in the bank along with annotated information, such as lifestyle and health history, for each donor. Researchers anxious to discover how breast cancer develops can now explore tissue samples and corresponding personal health and lifestyle information of each donor. This resource is believed to be the largest repository in the world of its kind.
Bryan Schneider, M.D., is investigating genetic and lifestyle clues to help explain why some women develop breast cancer and others do not. He has also identified genetic differences in how blood vessels that support tumor growth form, in order to identify women who are at increased risk for breast cancer. He was the first researcher to use data from the bio-repository developed by Dr. Storniolo and Dr. Clare, comparing 600 normal breast tissue specimens to 600 breast cancer specimens. Using the specimens, he found two distinct biomarkers for angiogenesis, or blood vessel formation.
The initiative for Monet Bowling, M.D., a breast surgeon who is one of the youngest team members, is to recruit minorities and young women to become involved in investigational studies. Her studies are focused on why these two particular groups are typically diagnosed with higher stage, more advanced disease than other profile groups.
Improving and Individualizing Treatment:
An increased understanding of the molecular identities of each woman’s breast cancer is leading to the design of new, individualized treatments for women with recurrent disease. Dr. Sledge continues to lead the country in this important work resulting in more effective treatments with fewer side effects, and extending the lives of women with advanced breast cancer.
Dr. Sledge and Kathy Miller, M.D., have found that the drug, Avastin®, can help shrink breast cancer tumors. The drug works by denying breast cancer tumors life-sustaining blood flow, to actually shrink and stabilize tumors, thereby sustaining the lives of women and increasing their qualities of life significantly more than other therapies.
Dr. Miller will be leading a new breast cancer trial for women with lymphedema, a common side effect in breast cancer patients, that causes swelling in the arms and is currently untreatable. She will be using an angiogenesis drug, which she believes will decrease pressure in blood vessels and tumors in order to reduce swelling.
Collaborating with the Indiana University-Purdue University at Indianapolis Virtual Reality Laboratory, Dr. Miller and Dr. Clare are working to create 3-D images of blood vessels that connect to breast cancer tumors. They will study the images of blood vessels before, during and after therapy to learn how blood vessels are affected so that other strategies to attack blood-vessel growth can be developed.
Dr. Storniolo is the primary investigator of a trial using a drug currently approved for colon and rectal cancers. This particular treatment targets a protein that is thought to interfere with the growth of cancer cells. Dr. Storniolo believes that, when used in combination with chemotherapy, it may help metastatic breast cancer patients.
Harikrishna Nakshatri, Ph.D., isolates and studies breast cancer stem cells as potential treatment targets. His theory is that the stem cell is within the tumor mass but most likely escapes treatment because of its enhanced ability to survive. He also is working to determine if the type of stem cell (i.e. lung, bone, brain, etc.) predetermines where the cancer will metastasize. This research may be able to one day help doctors predict, at the time of initial surgery, whether the disease is likely to metastasize to the bone, lungs or brain, and design treatments to prevent metastasis.
With Dr. Sledge, Dr. Herbert is working to devise a method of treatment to kill off immortal breast cancer cells by targeting and disrupting telomerase activity. The vast majority of human cancers achieve immortality by expressing telomerase, making the creation of a telomerase inhibitor a potential anti-cancer therapy.
In order to address younger patients’ fertility concerns, Dr. Schneider is investigating why some chemotherapies can cause hot flashes and early menopause. His goal is to identify women, at the time of breast cancer diagnosis, who have specific genetic markers that may put them at high risk for these side effects. He is working on developing treatments that may block the action of these genes and/or the tumor receptors.
Daniela Matei, M.D., is a clinical oncologist who specializes in treating women at risk for both breast and ovarian cancer. She has an active laboratory that is pursuing new treatment options for women with late-stage ovarian cancer.
Robert Goulet, M.D., is opening a trial at the IU Simon Cancer Center to test new technology that allows for amplification of DNA, which in turn aids in rapid detection of cancer cells in the lymph nodes of breast cancer patients undergoing surgery. The goal is to use this technology during surgery to help surgeons determine the extent of lymph node removal, establish the appropriate tumor stage, and ultimately help physicians determine if patients should receive additional treatment.
“This program has surgeons and pathologists and oncologists and people who actually treat cancer. There are wonderful researchers all over the country, but in most environments there is a stand alone dynamic—we could be doing research that would never make it to the clinic,” shares Dr. Malkas as she describes the cohesiveness of this group. Her face lights up as she says, “I work with people whose hearts are right there. We all desperately want to do something about breast cancer.”
Editor's Note: Dr. Malkas has since moved on to continue her work at City of Hope’s Beckman Institute in California.
Sources: Interviews with/and reference materials provided by: Linda Malkas, Ph.D., George Sledge, M.D., Brittney-Shea Herbert, Ph.D., Kathy Miller, M.D., Daniela Matei, M.D., Monet Bowling, M.D., Anna Marie Storniolo, M.D., Susan Clare, M.D., Ph.D., and Mary Maxwell, Director of Development, IU Simon Cancer Center. Additional information provided by: cancer.iu.edu/research