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Oncology update

Here are four major breakthroughs in the fight against cancer that recently took place at Children's Hospital Boston and the Dana-Farber Cancer Institute, joined together as Dana-Farber/Children's Cancer Care.

Finding cancer's fingerprint
In the Brain Tumor Clinic at Children's Hospital Boston, Scott Pomeroy, MD, PhD, associate in Neurology, sees cancer patients with learning disabilities, hearing problems and cataracts, all because the treatment they received for medulloblastomas, the most common type of malignant brain tumor in childhood, also damaged healthy parts of their brains.

Three years ago, Pomeroy turned to Todd Golub, MD, assistant in Medicine at Children's and an oncologist from the Dana-Farber Cancer Institute, to see if together they could treat patients' tumors without destroying the good tissue around them. Golub had developed a technique called microarray expression profiling, which determines the genetic "fingerprint" of individual cancer types, and together they found that the technology can accurately identify different types of brain tumors; but that's not all. "Much more important," says Pomeroy, "we are able to predict, at the time of the original diagnosis, the clinical outcome of medulloblastomas with much greater accuracy than is currently possible."

This allows physicians to identify not only the patients who have poor prognoses and will need aggressive therapy, but also the "good risk" patients whose tumors will respond to lower levels of radiation and chemotherapy, thereby killing the cancer cells while leaving healthy tissue alone.

The results of the study were published in the journal Nature in January, but Golub and Pomeroy see this as only a first step. "It's important not only for medulloblastoma," says Golub, "it also suggests that such signatures are likely to be detectable for other cancers as well."

NCI grant aids fight against ALL
In the 55 years since the first successful remission of pediatric leukemia occurred at Children's Hospital Boston, the combined pediatric cancer program known as Dana-Farber Children's Hospital Cancer Care (DF/CHCC), has led the world in survival rates for children with acute lymphoblastic leukemia (ALL), the most common childhood malignancy.

A new five-year $15.6 million grant from the National Cancer Institute will help that success continue.

Stephen Sallan, MD, chief medical officer of DF/CHCC, says the grant will have a profound effect on ALL research. "Although we've made vast improvements in our ability to treat this disease—to the point where more than 80 percent of all children are now cured—we need to get cure rates even higher and reduce the toxic side effects of current treatments."

ALL strikes about 1,500 children a year in the United States. It occurs when bone marrow loses the ability to produce enough red and white blood cells and platelets, causing patients to have fever, fatigue, aching joints and persistent infections. Below are brief descriptions of the seven projects funded by the grant.

  • Studying whether patients whose cells express the TEL/AML1 gene (more than 90 percent of whom are long-term survivors) can be treated differently than those without it.
  • Studying the genetics of leukemia in infants, who have only a 50 percent cure rate for ALL.
  • Comparing standard ALL to T cell ALL, a particularly aggressive type of leukemia. T cell ALL patients who express a certain gene have a cure rate of 70 percent, compared with a 20 to 30 percent rate in those without it.
  • Comparing genetic patterns in different types of ALL and looking for new therapies where genetic differences are found.
  • Improving the ability to detect leukemia cells in patients who otherwise test disease-free.
  • Overcoming the ability of ALL cells to become invisible to the body's immune system by "training" immune cells to recognize leukemia cells. Immune cells are then duplicated hundreds of thousands of times and injected into patients.
  • Trying to increase five-year cure rates for ALL beyond the current level of 83 percent, with a focus on finding more effective drugs or drug combinations.

—With contributions from Robert Levy of DFCI.

Answers on new cancers
In the journal Cancer last fall, researchers at Children's Hospital Boston reported on an aggressive new type of cancer that affects the upper respiratory tract of young patients, predominantly girls, and usually results in a rapidly fatal course. The cancer is known as t(15;19) carcinoma because of the abnormality on chromosomes 15 and 19 that causes it.

Sara Vargas, MD, assistant in Pathology, and her colleague Antonio Perez-Atayde, MD, director of Surgical Pathology, found the new cancer when examining biopsy specimens from two adolescent girls who died only weeks after diagnosis. The abnormalities had not been seen previously at Children's, but a handful of patients with the same problem were described at other institutions. By putting those cases together with the Children's findings, a specific, all-new syndrome emerged.

Perez-Atayde says the technique used to discover the disease, known as cytogenic analysis, has revolutionized the way researchers diagnose and classify tumors, and has provided new insight into how cancer originates, progresses and can potentially be controlled.

New technology also played a key role in the diagnosis of a new leukemia. Scott Armstrong, MD, attending in Oncology, was treating a 19-month-old patient for ALL when he found that the child's cells contained a unique chromosomal abnormality. Using gene expression profiling, which enables researchers to review as many as 12,000 genes at a time, Armstrong and his colleagues compared the leukemic cells with the abnormality to those without it. They found a very different genetic profile than either ALL or acute myelogenous leukemia, and realized the abnormality represented an entirely different leukemia, one they called mixed lineage leukemia, or MLL.

"This is what genomics and gene expression technology have to offer," says Armstrong. "If we can develop a drug based on this, it will be one of the first times this technology has been directly applicable to patients."


Dream
is published by Children's Hospital Boston. © 2005
Children's Hospital Boston. All rights reserved.