Creating new tools to fight the toughest cancers

How do you outsmart the toughest-to-treat cancers? You drill down to the genetics of not only the patient but also his or her cancer cells so you can deliver powerful, personalized care. You train bone marrow cells before transplantation so that they’re programmed to fight deadly infections and kill cancer cells. You study how the disease and treatment really impact the child and the family so you can maximize everyone’s quality of life.

Thanks to a $10 million gift from the MACC Fund, these and other exciting areas of pediatric cancer research will continue to advance at the MACC Fund Center at Children’s Hospital of Wisconsin. The gift, which will be used specifically to further research on cancer, bone marrow transplants and cellular therapies, is the latest in an ongoing partnership between the MACC Fund and Children’s Hospital of Wisconsin that spans more than 30 years.

“Having the support of the MACC Fund allows us to continue to fight cancer and blood disorders, to learn more about these diseases and to improve the outcomes and quality of life of our patients,” says the Marcio Malogolowkin, MD, director of the MACC Fund Center.

The latest gift builds upon an already strong foundation. Over the past five years, the MACC Fund Center has developed a vigorous clinical trial program led by Michael E. Kelly, MD, PhD, director of the Cancer program. The program gives patients and their families critical access to new potential treatments.

While childhood cancers make up only 1 percent of new cancer cases diagnosed every year, cancer can impact a child’s life for decades, making it all the more important to research aspects such as long-term side effects of treatments, Dr. Malogolowkin notes.

Eighty percent of pediatric cancer patients become long-term survivors. For the remaining 20 percent, the disease never goes away or continues to come back.

“We need to better understand the mechanisms of those diseases, why certain tumors reoccur and others don’t,” Dr. Malogolowkin says. “And the only way to be able to do that is to collect, bank and analyze these specimens, to better understand the genetic makeup of these diseases so we can discover new therapeutic approaches, new drugs, new pathways. … Then we can take those discoveries to the national level.”

One goal is to improve the effectiveness and safety of bone marrow transplants.

“Today, the only effective immune therapy against cancer is bone marrow transplant,” Dr. Malogolowkin says. “You give a very, very high dose of chemotherapy, so you’re trying to wipe out the cancer, but then you’re putting in bone marrow cells that have the ability to fight against cancer cells.”

But that approach comes with certain risks — resistant cancer cells can find a way to escape the deluge of chemotherapy; the immune system can mistakenly recognize the patient’s body as a foreign element and go on the attack, a serious condition called graft vs. host disease; or patients can contract deadly infections while their immune system is still suppressed.

So investigators at Children’s Hospital of Wisconsin and the Medical College of Wisconsin are training hematopoietic stem cells to work in a safer, more effective way. Julie-An Talano, MD, and Carolyn Keever-Taylor, PhD, are training donor cells to fight specific viral diseases that patients are at high risk of getting after a bone marrow transplant. Monica Thakar, MD, is leading a study that selects a specific kind of immune cells — known as natural killer cells — that can target only the cancer cells without the risk of graft vs. host disease. Both techniques now are being tested in clinical trials at Children’s Hospital.

Researchers are also using a targeted approach to customize cancer care.

“We know that each patient is an individual with his or her own genetic makeup, and so is cancer. Understanding the genetic makeup of individuals and their cancer will help us do what is the ‘holy grail’ of modern cancer therapy, what has been labeled as personal therapy,” Dr. Malogolowkin says. “So instead of coming in with a shotgun approach you can choose the therapies that will be most efficacious for those diseases.”

For example, doctors can learn in advance whether a drug is too toxic for a particular patient because he can’t metabolize it properly or whether a patient can tolerate an increased dosage. And because every cancer is different, researchers can learn whether cancer cells have intrinsic defense mechanisms against certain treatments and choose their weapons accordingly. While personalized therapy probably wouldn’t be necessary for every patient, it could be incredibly valuable for the toughest cases.

But it’s also important to care for more than just a patient’s cancer. Julie Panepinto, MSPH, MD, is leading a study on patient-reported outcomes in cancer and bone marrow patients with the end goal of providing better support for children and their families.

“Because our patients are long-term survivors, and we know that our therapies are associated with some side effects, outcomes for us are more than just alive or dead, free of disease or not,” Malogolowkin says. “What is the impact of having the disease, of being treated, on your day-to-day life? How does it impact your ability to function as a normal child?”

Understanding the answers to those questions is key to ensuring that kids with cancer get the best care possible — and researchers at the MACC Fund Center won’t stop until that happens.