Curing Childhood Cancer and Other Diseases

Starting with a Single Molecule

Known as a master of medical discoveries, Kevin Bunting, Ph.D., currently is studying a single molecule that may help him achieve his goal of curing several childhood cancers and other diseases.

Dr. Bunting is a researcher at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, as well as Professor of Pediatrics at Emory University School of Medicine.

The focus of Dr. Bunting’s research is to understand how healthy and abnormal blood stem cells develop at the molecular level. He is working toward finding less toxic, more therapeutic treatment options for childhood cancers and other diseases that affect much of the population.

For example, in children from birth to age 14, leukemia accounts for about 31 percent of all cancers. Meanwhile, 400 infants are born with hemophilia each year, and sickle cell disease affects between 70,000 and 100,000 Americans annually. 

Today, the most common form of treatment for these diseases is radiation, which often destroys both the abnormal cells and surrounding healthy cells. Patients are left with dangerously low levels of immunity and extremely toxic side effects.

Dr. Bunting specializes in studying a molecule called STAT5, which shows great promise as a treatment that would greatly reduce unwanted side effects, like those associated with radiation. In fact, STAT5 could lead to a revolutionary treatment of the previously mentioned childhood diseases, among many others.

Known as a transcription factor, the STAT5 molecule regulates the functions of many other important molecules. These other molecules determine how well stem cells reside in bone marrow and how quickly they duplicate.

By removing or changing STAT5 in some way, Dr. Bunting has discovered the remaining STAT5-deficient cells can survive and continue to reproduce healthy cells—while losing the ability to reproduce abnormal cells.

Dr. Bunting quickly realized the potential magnitude of this discovery—to develop an actual cure for hematology and oncology cancers and illnesses in children. Because this treatment would effectively cure illnesses without the harsh effects of radiation, the cure rates of cancer and blood disorders—like leukemia, hemophilia and sickle cell disease—could be dramatically improved.

By eliminating STAT5, it even may be possible to graft healthy stem cells where cancerous tissues were previously located. Dr. Bunting said of this technique, “I study how you get existing stem cells to leave and die and allow the new ones to take their place—basically it’s musical chairs.” 

If STAT5 molecules can be reduced or eliminated in bone marrow, it would allow a physician to prune out only the bad stem cells (like a gardener) instead of bulldozing through both the bad and surrounding healthy stem cells (like a landscaper).

“Right now,” said Dr. Bunting, “radiation wipes out everything.” But this potential new treatment would reverse this unwanted effect, producing a much less toxic treatment that does not damage the DNA. In the future, it could also have many more medical uses. For example, it could be adapted to reduce the risk of rejection in solid organ transplants.

Dr. Bunting also hopes to extend this research through a CURE grant proposal focusing on STAT5. In his proposal, Dr. Bunting aims to characterize the role of STAT5 in tumor cells and test drug combinations on patient samples to test their effectiveness. His stance is that further testing on STAT5 is needed to optimize the therapies being used on pediatric patients with cancer.

As part of his ongoing research, Dr. Bunting regularly shares information with the several other labs also studying STAT5 across the country. By doing this, researchers can share information, avoid duplicating their efforts and shorten the amount of time it will take to find a viable, STAT5-based treatment option.

Since his discovery of the role of STAT5, Dr. Bunting has been studying readily available drugs to find candidates that can recreate the STAT5-deficient effect in cells. Once these candidate drugs are identified, Dr. Bunting will move into the next phase of research, live test subject studies. Dr. Bunting hopes to identify new therapeutic drug combinations that can mimic a STAT5 deficiency in the blood stem cells, thereby curing these diseases in live test subjects.

Other doctors are now basing their research efforts on Dr. Bunting’s initial findings regarding STAT5. For example, Zhengqi Wang, Ph.D., is also studying the STAT5 molecule and its regulation of healthy versus abnormal stem cells. Like Dr. Bunting, Dr. Wang is a researcher at the Aflac Cancer Center and Professor of Pediatrics at Emory University School of Medicine.

Dr. Wang’s research builds on Dr. Bunting’s work by focusing specifically on STAT5-driven leukemias. Dr. Wang hopes to identify new therapeutic drug combinations that can mimic a STAT5 deficiency in blood stem cells that cures leukemia.

Drs. Bunting and Wang came to the Aflac Cancer Center from the Division of Hematology and Oncology in the Department of Medicine at Case Western Reserve University School of Medicine.

“There are several benefits to being here,” Dr. Bunting said of the move to the Aflac Cancer Center of Children’s. “But one of the best is that they offer a full-spectrum program, from basic science to the clinical applications. It’s a great opportunity.” 

Drs. Bunting and Wang both were recognized as 2008 Program Leaders of the Year for the Stem Cell and Hematologic/Malignancies Program at Case Western Reserve University School of Medicine.

WorkingTogether
  • Other doctors are now basing their research efforts on Dr. Bunting’s initial findings regarding STAT5. For example, Zhengqi Wang, Ph.D., is also studying the STAT5 molecule and its regulation of healthy versus abnormal stem cells. Like Dr. Bunting, Dr. Wang is a researcher at the Aflac Cancer Center of Children’s and Professor of Pediatrics at Emory University School of Medicine.

    Dr. Wang’s research builds on Dr. Bunting’s work by focusing specifically on STAT5-driven leukemias. Dr. Wang hopes to identify new therapeutic drug combinations that can mimic a STAT5 deficiency in blood stem cells that cures leukemia.