Cancer. It’s been called The Emperor of All Maladies.* The scourge of man, apernicious, spreading evil.
“The Big C.”
At the School of Medicine’s Simmons Cancer Institute (SCI), researchers are taking action against cancer by unlocking the secrets of how cancer works. “Our researchers are on the cutting edge of developing a deeper understanding of the biology of cancer,” says John Godwin, M.D., professor and chief of the hematology and oncology division in the Department of Internal Medicine and associate director of SCI. These new perspectives in the science of cancer research are providing more promising treatments and better quality of life for cancer patients and may be the key to stopping cancer altogether.
SCI clinical trials apply ground-breaking research to patient care.
On-site researchers striving to unfold the secrets of the biology of each cancer give SCI an advantage over any other cancer treatment center in the area. “The discoveries made by our cancer researchers in the laboratories may have more meaningful applications because our clinicians are engaged in reviewing the research,” says K. Thomas Robbins, M.D., director of the Simmons Cancer Institute.
Many of these direct-to-patient applications come in the form of clinical trials, which take therapies that have been tested in the lab and evaluate them in the clinical setting. Some trials test the effectiveness of new medicines for cancer treatments, while others evaluate new treatments over traditional options.
Patients who participate in cancer clinical trials have an opportunity to provide researchers with knowledge about cancer and to help in the development of improved cancer treatments while receiving expert medical care. If a new treatment proves effective in a study, it may become a standard treatment that can help others.
SCI’s clinical trials cover multiple cancers including brain, breast, renal, pancreatic, colorectal, prostate, renal and sarcoma. “All of our physicians use these clinical trials where appropriate to offer the best available treatment options to cancer patients,” says Dr. Godwin.
Visitors at SCI often see a small, brightly covered booklet peeking out of the pockets of the white coats of the doctors. Because SCI has hundreds of trials taking place at once, a booklet is printed each month with a description of every open trial. It is their go-to guide. “Whenever we see a new patient, our instant reflex is to go to the book to see if a trial is open,” says Krishna A. Rao, M.D., Ph.D., associate professor of internal medicine and member of the SCI team. “If the patient has relapsed, is in remission, or if there is another drug that we can offer them, we can find that too.”
With state-of-the-art resources at their fingertips, SCI’s clinicians are able to work with the researchers, encouraging them to investigate specific clinical problems that would otherwise remain unsolved. They are also able to delve into their own research, investigating, designing and conducting new clinical trials. Currently, eight SCI doctors are principle investigators for their own clinical trials.
HITTING THE TARGET
Finding the target, developing the therapy and saving lives makes SCI a preference in cancer care.
Determining the best way to beat a particular cancer can also be as complex as the disease itself. SCI takes a team approach to cancer care by developing an individual patient treatment plan based on the best available evidence. This plan may incorporate clinical trials. “There is not just a single type of lung cancer or breast cancer; there’s a whole host of different flavors and types,” says Dr. Rao. As researchers begin to understand the biology of each cancer type, they are better able to determine how to fight it.
Researchers have found that creating a drug to target a specific cancer pathway is easier than creating a “super-drug” to defeat multiple cancers. This means that more drugs will be available to treat cancer, but they will target certain cancer types. “We’re beginning to design many, many drugs for those many, many types of cancer,” says Dr. Rao.
According to the National Cancer Institute, these targeted therapies, also called by other names such as small molecules or molecularly targeted drugs, focus on the changes that are specific to cancer at the molecular and cellular level. For this reason, these treatment options might be more effective at attacking the cancer cells and less harmful to normal cells than traditional treatments such as chemotherapy. Because they are comparatively non-toxic, small molecules offer options to patients who may not tolerate conventional chemotherapy.
The relatively miniscule size of targeted therapies may allow them to enter areas of the body where chemotherapy medications have failed. For example, the brain has a protective barrier to inhibit toxins from entering; however, this same barrier also can block many beneficial chemotherapy medications, making metastatic brain cancer difficult to treat. Metastatic cancer of the blood, bone or spinal fluid also presents difficulties for doctors, but research to find targets for these metastatic cancers is making progress.
Kounosuke Watabe, Ph.D., professor of medical microbiology, immunology and cell biology, strives to find agents to attack the particular targets for metastatic cancers. Dr. Watabe’s current research shows promise for some future targeted therapies in the areas of brain metastasis of breast cancer and bone metastasis of breast and prostate cancers.
One promising study uses a natural protein called BMP7 to keep the tumor cell dormant in bone metastasis of prostate cancer. By developing a targeted therapy that mimics the function of BMP7, researchers can target tumors with fewer side effects than chemotherapy. “Targeted therapy treats metastatic cancer like a chronic disease,” says Dr. Watabe. “It’s almost the same as a cure because people can live longer with a better quality of life.” Dr. Watabe hopes for an rapid translation of this cancer research to a clinical trial since BMP7 has already been approved by the United States Food and Drug Administration for use in bone fractures.
Targeted therapies are being used in clinical trials. For example, a drug called erlotinib (Tarceva®) was first approved by the United States Food and Drug Administration in April 2010 after many clinical trials showed its benefits for treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Unlike any other medication, this once-a-day pill effectively slows the tumors of non-small cell lung cancer with minimal side effects.
According to Dr. Godwin, approximately 5 percent of patients who are diagnosed with non-small cell lung carcinoma (NSCLC) have a specific mutation that can be targeted by erlotinib (Tarceva®). “After a lot of research we discovered that this mutation is the driver in these cases of NSCLC,” says Dr. Godwin. “Now we have a target – and we have a drug that hits that target. For this cancer, one pill works better than chemotherapy.”
Donna Brown, 67, of Springfield was diagnosed with NSCLC, and test results showed that she has the specific mutation that can be targeted by Tarceva®. Brown was diagnosed with lung cancer in 2006 and treated with curative intent surgery only to have her cancer return in the summer of 2011 and metastasize to her brain and spinal fluid. Doctors didn’t expect her to survive long enough to celebrate Thanksgiving. She returned to Springfield for treatment at SCI after whole brain radiation at Mayo Clinic proved ineffective. “At that time I was told to call hospice, that there was nothing else they could do for my cancer type,” says Brown.
When she returned to Springfield, Dr. Godwin encouraged her to try Tarceva®, and she finally agreed. “I thought that if I was only going to live a short time, I wanted it to be a good life, and I could deal with these side effects,” says Brown. The targeted therapy has allowed her body to rebound from previous treatments and grow stronger. Prior to taking Tarceva®, Brown was sleeping 20 hours a day and using a wheelchair to come to her appointments at SCI. “Now, my breathing is better, I have less coughing, I’m not as tired, and I can walk much more easily,” Brown states.
DEFENDING FROM WITHIN
Using immunotherapy allows the body’s own defense mechanisms to combat cancer.
Though some subsets of cancer are proving unresponsive to targeted therapies, new scientific knowledge suggests that the patient’s own body may be effective in treating some of these cancers. “One of the best treatment options with long-term benefits is to harness the body’s own immune system to kill the cancer,” says Andrew Wilber, Ph.D., assistant professor of medical microbiology, immunology, and cell biology. “This can be done either by stimulating the body’s immune system or by giving the body synthetic proteins found in the immune system in order to train it to identify cancer cells and destroy them.”
Dr. Wilber and other scientists at SIU continually strive to find more ways to combat the immunosuppressive mechanisms taking place in the tumor environment. However, since cancer cells are a part of one’s own cells, the body resists fighting against itself. “We would like to interfere with the tumor so that it doesn’t produce the immune-suppressing molecules but instead lets the immune system act at its normal potential,” says Dr. Wilber.
According to the American Cancer Society, immunotherapy tends to work better when used with or after other treatments. Like targeted therapies, immunotherapy produces fewer and less severe side effects than standard treatments. Smaller or earlier stage cancers also respond better to treatments using immunotherapy.
SCI is the only treatment center in central Illinois that is opening a trial for an immunotherapy used to treat both small cell and non-small cell lung carcinoma. A drug called Ipilimumab (Yervoy™) was first approved by the United States Food and Drug Administration in March 2011 for the treatment of metastatic melanoma after research and clinical trials proved its effectiveness. Yervoy™ works by blocking the inhibitory signal of a molecule found on t-cells that plays a critical role in regulating the body’s natural immune response. According to Dr. Godwin, its great promise in treating metastatic melanoma has led to studies of its use in combination with chemotherapy for the treatment of non-small lung carcinoma. “This drug produces remissions we’ve never seen before,” says Dr. Godwin.
Research in the labs at the School of Medicine and clinical trials developed by physicians at SIU enable SCI to open trials using innovative treatments such as Yervoy™. Current clinical trials are no longer empiric combinations of cancer poisoning chemotherapies, rather they are treatments relying on a deeper understanding of the variety of cancer-driving mutations. Clinical trials with targeted therapies and immunotherapies are just a few of the remarkable advances made possible because of research. “Research into the basic science of cancer will ultimately give us insights and provide the next wave of cures,” says Dr. Rao. As these new therapies progress, doctors and researchers alike hope to put an end to cancer’s reign.
*The Emperor of All Maladies by Siddhartha Mukherjee