The Director of the National Cancer Institute offered the challenge: develop a molecular classification system for tumors. Those who study childhood cancer prepared a proposal at once, since children are the perfect model for such work. That’s because it is usually just a single catastrophic genomic insult which leads to childhood cancer, while adult cases may be less straightforward, with factors such as smoking and other illnesses a part of the equation.
This timely response to the challenge was successful: close to $8 million has been awarded for five years of work on “Childhood Sarcomas” by collaborators at Childrens Hospital Los Angeles and USC, The University of British Columbia, Cal Tech, JPL, and the Children’s Oncology Group (COG).
Building on data now becoming available from the recent progress of the Human Genome Project, the study will perform micro-array gene expression analysis of every available sarcoma specimen from children treated by the Children’s Oncology Group over the next five years, expected to be about 500 a year. An already-completed smaller study of 45 patients at Childrens Hospital Los Angeles has shown that gene expression profiles can be used to diagnose and predict the class of children’s tumors. More significantly, this approach was also able to predict outcome with far greater precision than any other existing predictor.
How is micro-array analysis conducted? Don’t ask! Someone may try to explain to you that rows of complementary gene copies are arrayed in a microscopic pattern. Then real genes from tumor tissue — after labeling with a fluorescent dye — are fixed to the copies. The resulting pattern of “hits” registered on a gene chip is scanned by a computer that generates a gene expression profile of up to 60,000 human genes, all within minutes.
More important than how it is done is what it means for future cancer patients. The results at the completion of this landmark study could lead to a huge improvement in cancer care, for adults as well as children, including:
- Precise categorization of the tumor, and a more relevant diagnosis
- More accurate assignment of cases to high risk or low risk categories
- Improved prediction of the possibility of relapse or non-responsiveness to chemotherapy, and therefore more targeted therapies
- Improved predictability of outcome
- Greater basic understanding of the basic biology of tumors through identification of abnormally expressed genes
- New alternative therapies, based on specific gene target information, for new drug development
Pharmaceutical companies are already eager to develop products that target specific genes. “This is just the beginning of a new field of targeted therapy,” says Timothy Triche, MD, Pathologist In Chief at Childrens Hospital Los Angeles and Professor of Pathology and Pediatrics at the USC Keck School of Medicine.
Triche notes, “The microscope has been around for 300 years. The current way of diagnosing tumors and predicting their behavior is primitive by today’s standards. Tumors are generally placed into a group just because they look alike under a microscope. But green apples get mixed in with red apples, and so on.”
He says, “In the future, tumor categories will be based on microscopic diagnostic criteria, as well as gene expression and other molecular genetic criteria. We will correlate those observations with the results of gene expression profiles, and see what works. Ultimately, we will refine the criteria used with the microscope, as well. In addition, we’ll get an instant snapshot of every gene in that tumor’s genome and what it’s doing, and what turns it on or off. Based on their gene expression profiles, they will fall into precise categories, which we hope will identify the optimal therapy.”
By the end of the five-year project, every human gene will be in the array. “We now look at 13,000 genes at a time. We will soon be able to see 60,000 at a time. And there are only 100,000 at the most. So soon we will look at every gene,” Triche predicts.
This will have a profound effect on the whole field of cancer management. “All of us involved in the management of children with cancer, or anyone with cancer for that matter, hope this new approach will ultimately improve the outcome and minimize the consequences for patients,” says Triche. This new study promises to reveal the newest and best treatments for childhood cancer tumors in the near future.
Copyright, National Childhood Cancer Foundation. Republished with permission from National Childhood Cancer Foundation. No further reproduction or redistribution is permitted without the expressed written consent of National Childhood Cancer Foundation.