In a large, seven-floor building, adjacent to The Nebraska Medical Center is the UNMC Eppley Cancer Center’s Eppley Institute for Research where internationally recognized cancer researchers are fighting the battle against cancer with an entirely different arsenal– that of test tubes, Petri dishes, microscopes and high-tech machines that sort cells, identify DNA and separate gene molecules.

As one of only sixty National Cancer Institute (NCI)-designated cancer centers in the United States, the Eppley Cancer Center is nationally and internationally recognized for its groundbreaking work in cancer research, treatment, and patient care and has recently seen a tripling of its funding from the National Institutes of Health and other government sources.

Oncologist Kenneth Cowan, MD, director of the Eppley Institute for Research and Cancer and director of UNMC Eppley Cancer Center, leads hundreds of basic research studies and clinical trials to help researchers find the answers to such questions as to what turns certain genes on and off, the molecular mechanism that leads cells to become resistant to anti-cancer therapy, how DNA is damaged, what causes cells to mutate and how. The answers to these types of questions are key to bringing novel therapies developed in the lab to patients in clinical trials, providing our patients access to the newest treatments and improved patient outcomes.

Ying Yan, PhD., Dr. Cowan’s research assistant for the past eight years, talks enthusiastically about their progress in understanding the function of the BRCA-1 gene, a gene that increases a woman’s risk of developing breast cancer by 95 percent. Of course, we are still a long way from seeing this translate into a cancer prevention drug, but the research is promising and Dr. Yan is hopeful that their research may someday help prevent cancer in thousands of women in the future. “This is what makes this job so rewarding,” she says. “My father died of cancer and knowing that I may be able to have an impact on helping others survive the disease in the future – that’s gratifying.”

Much of Dr. Cowan’s breast cancer research focuses on the development of new forms of treatment called targeted therapies that are being used in combination with traditional treatments to improve outcomes for breast cancer patients.

Targeted therapies refer to drug treatments that attack tumors without harming healthy tissue. They are categorized into three major types based on the method in which they attack the tumor: aromatose inhibitors, HER-2 therapy and anti-angiogenesis drugs.
Doctors use these therapies by first developing a customized care plan based on the biology of a patient’s cancer – what it is, how big it is and how it acts. Depending on how the cancer has been classified, doctors then treat the cancer with traditional chemotherapy and surgical techniques, and then add targeted therapies to the mix.

Researchers like Dr. Cowan, and his colleagues, including Dr. Reed and Dr. James Talmadge, are involved in one of the most promising and cutting edge forms of cancer research called gene therapy, which is being funded by a grant from the National Cancer Institute. Researchers have pinpointed a specific protein – P53 – that is found in all cancers. This protein, says Dr. Cowan, is responsible for altering genes, causing them to become genetically unstable. This causes other mutations and can eventually lead to cancer. Gene therapy involves pinpointing specific genes, that when injected into cells through a carrier molecule called a vector, will then unload their genetic material and attack cancer cells – with the hopes of killing them. Dr. Cowan says researchers in Florida currently are seeing promising results with the use of the P53 vaccine in treating lung cancer patients.

Dr. Cowan also talks enthusiastically about another area of groundbreaking research that involves using a person’s own white blood immune cells to generate an immune response against cancer cells. The process involves manufacturing dendritic cells – immune cells, which when activated, identify proteins that are foreign and help form an immune response to destroy them. The hope is that when these cells are injected into the tumor, they will help the immune system form an immune response against the tumor and eliminate the cancer tumor.

“The future of breast cancer lies within research,” says Dr. Reed, who has been involved in conducting studies since her early days of practice. “If it weren’t for trials and research, we wouldn’t have on-going improvements in treatments. If you can get large numbers of people enrolled in clinical trials, then you can make big advances.” Dr. Reed says she offers an investigational choice to all of her patients. “Providing patients with investigational choices is an opportunity to get tomorrow’s best therapy today,” she says. “We wouldn’t be where we are today if it weren’t for people being involved in research studies.”

Targeted therapies hold promising hope for the future of breast cancer
A woman diagnosed with breast cancer has more treatment options than ever before. Evidence is mounting that newer forms of treatment called targeted therapies, used in combination with traditional treatments, are improving outcomes for breast cancer patients. Targeted therapies refer to treatments that attack tumors with minimal harm to healthy tissue. They are categorized into three major types based on the method in which they attack the tumor: aromatose inhibitors, HER-2 therapy and anti-angiogenesis drugs.

For the past 10 years, women whose tumors are hormone-receptor positive, meaning they are fueled by the hormones estrogen and progesterone, have been treated with a hormonal drug called tamoxifen for approximately five years after breast cancer surgery. The drug works by reducing estrogen’s ability to fuel cancer growth. Treatment of patients with hormone sensitive breast cancer with tamoxifen reduced their risk of recurrence by 25 percent. More recently, a new class of drugs called aromatase inhibitors have been found to be significantly more effective than tamoxifen in reducing the ability of these cancers to grow. Aromatase inhibitors in postmenopausal patients with estrogen-receptor positive breast cancer are now considered first line of adjuvant therapy.

New hope has also arrived for women who develop an aggressive class of cancer tumors that produce too much of a gene called HER-2. These women tend to be younger and until recently, had little or no options after completing chemotherapy. That was the standard of care until the monoclonal antibody drug Herceptin was introduced to the market. The drug works by slowing or halting the growth of cancer cells with large amounts of HER-2. With 52 weeks of infusion with this antibody, more of these women are likely to be cured of their cancer.

Another class of drugs not limited to a specific type of tumor are anti-angiogenesis drugs. These drugs work by inhibiting the formation of new blood vessels that feed tumors. “They do not make the tumor go away, but they have been very effective in preventing their growth,” says James Talmadge, PhD, research specialist. One of these drugs, called Avastin, has been effective in treating colorectal cancer, and has recently shown success in prolonging survival rates in breast cancer as well.

The development of vaccines is another area of drug research that is showing potential for fighting breast cancer. “We know they work and they have the advantage of being non-toxic,” says Dr. Talmadge. “The problem is that chemotherapy inhibits the activity of vaccines.” Even so, there are several vaccines in clinical trials that are showing promise. “I think we will begin seeing success with more vaccines in the future,” says Dr. Talmadge. “Currently, there is tremendous excitement about a vaccine that has been shown to prevent the development of cervical cancer in 97 percent of women. We anticipate seeing additional success in the development of vaccines to prevent and treat cancer in the future. These new drug therapies are having a significant impact on our ability to fight breast cancer and hold much promise for the future of breast cancer treatment.”