Nai-Kong V. Cheung, head of the neuroblastoma program in Memorial Sloan-Kettering Cancer Center's
Department of Pediatrics and Enid A. Haupt Chair in Pediatric Oncology, believes that a better understanding
of tumors will lead to better treatments for children with cancer.
I believe that in pediatric oncology, we face a different kind of challenge. When treating a child with a cancer
such as neuroblastoma, which originates from primitive cells of the sympathetic nervous system, we have to
deal with the immediate threat of the disease, but then we also have to consider the long-term effects of the
treatment — these patients have their whole lives ahead of them. What we call a "success" is a qualified
statement. Some neuroblastoma tumors are metastatic and require intensive treatments; others are less
threatening and can actually disappear or remain unchanged with minimal or no treatment.
Four years before I joined the Center in 1987, I began to devote my professional life, from the laboratory
bench to the patient's bedside, to the treatment of neuroblastoma. For two decades, I have witnessed the
heavy toll on children and families affected by this cancer. Our priority is to identify the 50 percent of patients
who do not need cytotoxic treatment such as radiation or chemotherapy, while for the other 50 percent, to
design treatments that are not only more effective, but also more specific.
Department of Pediatrics and Enid A. Haupt Chair in Pediatric Oncology, believes that a better understanding
of tumors will lead to better treatments for children with cancer.
I believe that in pediatric oncology, we face a different kind of challenge. When treating a child with a cancer
such as neuroblastoma, which originates from primitive cells of the sympathetic nervous system, we have to
deal with the immediate threat of the disease, but then we also have to consider the long-term effects of the
treatment — these patients have their whole lives ahead of them. What we call a "success" is a qualified
statement. Some neuroblastoma tumors are metastatic and require intensive treatments; others are less
threatening and can actually disappear or remain unchanged with minimal or no treatment.
Four years before I joined the Center in 1987, I began to devote my professional life, from the laboratory
bench to the patient's bedside, to the treatment of neuroblastoma. For two decades, I have witnessed the
heavy toll on children and families affected by this cancer. Our priority is to identify the 50 percent of patients
who do not need cytotoxic treatment such as radiation or chemotherapy, while for the other 50 percent, to
design treatments that are not only more effective, but also more specific.
BANDofPARENTS bound by hope
Interview with Nai-Kong V. Cheung
Dr. Nai-Kong V. Cheung,
Head, Neuroblastoma Program;
Enid A. Haupt Chair in Pediatric Oncology
With the help of sophisticated imaging and the tools of molecular pathology, our neuroblastoma team can now, with 95 percent certainty, identify
those patients whose tumors do not need cytotoxic therapy and achieve a greater than 90 percent survival rate. This is a substantial
improvement compared to a decade ago, and we are excited by a worldwide effort to validate these approaches in large clinical trials. Sparing
children unnecessary therapy is always a blessing, since treatment-related issues (medical cost, out-of-pocket expenses, time away from work,
issues with other children in the family, and marital problems) can cripple even the strongest family. However, the five percent of patients whose
tumors only masquerade as low-risk is a constant reminder that further understanding of tumor biology is necessary. We are hopeful that
mapping the genetic makeup of these tumors will eventually eliminate these uncertainties and allow more accurate classifications and treatment
choices.
For the other 50 percent of neuroblastoma patients, those who do need aggressive therapy, we have also made substantial progress in recent
years. For more than a decade, we have utilized monoclonal antibodies to deliver therapy more selectively to these tumors. We take advantage
of the ability of these antibodies to activate white cells and complement proteins, as well as to carry radioisotopes to deliver radiation to kill
tumor cells. We continue to optimize the combination of chemotherapy, surgery, radiation, and immunotherapy for high-risk metastatic
neuroblastoma. More recently, we demonstrated that the combination of monoclonal antibody 3F8 plus GM-CSF (granulocyte macrophage
colony stimulating factor) is highly effective in destroying residual tumor cells in the bone marrow. While an antibody alone can prolong survival
for high-risk patients in their first or second remission, the addition of GM-CSF can further improve their odds.
Back in the laboratory, we continue to explore methods to increase the effectiveness and selectivity of antibody-based treatment strategies. For
example, we have identified beta-glucan derived from barley as a potential enhancer of antibody action against human tumors. We have also
genetically engineered monoclonal antibodies to improve their therapeutic ratio using a "two-step" targeting strategy, utilizing a fusion protein
called scFv-streptavidin that has two binding sites, one for the tumor and the second for a small molecule to carry therapeutic agents such as
radioisotopes, drugs, or biologics. We hope to test these scFv fusion proteins in the clinic in the very near future.
Because more than ten percent of treated patients return to us with isolated tumors in the brain or the surrounding cerebrospinal fluid, we are
developing more effective methods to treat or to prevent such occurrences. By injecting antibodies or antibody conjugates directly into the fluid,
we can kill tumor cells that hide there and thus escape chemotherapy. In early clinical studies, there were few serious side effects and some
patients have lived longer than expected. In an effort to further increase the selectivity and efficacy of such an approach, Leukemia Service
Chief David Scheinberg and I, both members of Memorial Sloan-Kettering's new Experimental Therapeutics Center, have teamed up to
investigate the use of "nanogenerators" carried by antibodies to kill tumor cells circulating in the cerebrospinal fluid. This method has great
potential, and it is a good example of how Memorial Sloan-Kettering researchers work together.
We continue to bridge our laboratory findings to the clinic, constructing new treatment protocols and offering hope for families whose children
have unusually aggressive tumors. Besides monoclonal antibodies and new chemotherapeutic agents, we are testing new classes of drugs,
such as arsenic trioxide. We are encouraged by its potential clinical benefit and the relatively mild side effects.
When I left my home in Hong Kong to attend college and eventually medical school in the United States, I embarked on a journey of hope for a
healthier world. Seeing children and their families stricken by neuroblastoma is heart-wrenching. Together, these special people and a large
team of health professionals at Memorial Hospital will continue to orchestrate a "Symphony of Hope," the theme of our recent neuroblastoma
survivors reunion celebration.
 | |  | |  | |  | |  | |  | |  | |  | |  | |  | |  |