Guest Update by Dr. Malcolm Smith

Initiative TARGETs Childhood Cancer

Although there has been an explosion in the development of molecularly targeted therapies, these advances have been largely limited to the treatment of adult cancers. The need for new treatment approaches for childhood cancers, however, is substantial. The dramatic improvements in outcome seen over the last several decades have slowed, and, in many cases, current treatment approaches for childhood cancers cause serious short- and long-term side effects.

To see that children do benefit from advances in molecularly targeted cancer therapeutics development, NCI and the Foundation for the National Institutes of Health (FNIH) have established the Childhood Cancer Therapeutically Applicable Research to Generate Effective Treatments, or TARGET, Initiative.

The TARGET Initiative is a public-private partnership to identify and validate therapeutic targets so that new, more effective treatments can be developed for children with cancer. Its immediate goal is to make major advances in identifying and validating therapeutic targets for two or more childhood cancers within 2 years of project initiation. FNIH will raise money from the private sector to augment NCI resources allotted for the initiative.

TARGET builds upon a workshop sponsored by NCI and the American Cancer Society in May 2005 that brought together scientists, advocates, and foundation and industry representatives to discuss the challenges in identifying effective new treatment approaches for children with cancer. It also builds upon the experience and expertise NCI has gained in working with the National Human Genome Research Institute to develop The Cancer Genome Atlas (TCGA) Pilot Project.

TARGET will have three primary areas of research focus. The first involves high-throughput array-based technologies to comprehensively characterize genomic and transcriptomic profiles for selected childhood cancers. The second will utilize gene resequencing to identify genes that are consistently altered in specific childhood cancers, as these genes represent strong candidates for therapeutic targeting. Finally, high-throughput RNA interference and small-molecule screening methods will be applied to identify and validate therapeutic targets.

A key principle in implementing this initiative is to leverage the investments NCI has already made in other programs and initiatives, including TCGA, the Strategic Partnering to Evaluate Cancer Signatures program, and the Children's Oncology Group (COG), which has an extensive collection of annotated tumor specimens. A subcommittee of the NCI Board of Scientific Advisors (BSA) will provide strong scientific oversight and direction for the initiative. The subcommittee met for the first time at the November BSA meeting, and will meet regularly to provide advice and feedback on the initiative's course.

TARGET will begin with a pilot project that will inform the larger initiative. The pilot - a collaboration involving COG, the University of New Mexico, St. Jude Children's Research Hospital, and NCI - will focus on identifying therapeutic targets for high-risk acute lymphoblastic leukemia (ALL). Already, high-resolution genomic and transcriptomic profiles are being obtained on approximately 240 ALL cases. These data will be used to select approximately 200 genes for resequencing, which should occur by mid-2007.

While TARGET is designed to benefit children with cancer, there may also be implications for adult cancer therapeutics development. The relatively simple genomic alterations of most childhood cancers may facilitate therapeutically relevant discoveries that could extend into the adult cancer setting.

With TARGET, we are engaging in a systematic application of state-of-the-art technologies to rapidly identify and validate therapeutic targets in childhood cancers. If successful, it will allow new, more effective treatment approaches to be developed, ensuring that children also will benefit from the ongoing revolution in cancer therapeutics development.