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Children’s research discovery aids in adult cancer drug development


The recent approval by FDA of an adult cancer therapy is 1 example of how children’s cancer research benefits patients of all ages.

The recent approval by FDA of an adult cancer therapy is 1 example of how children’s cancer research benefits patients of all ages.

FDA recently approved crizotinib (Xalkori, Pfizer) as a first targeted therapy for patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) that is locally advanced or metastatic. Crizotinib targets a malfunctioning gene that drives anaplastic large cell lymphoma (ALCL). It was discovered more than a decade ago by Stephan Morris, MD, then a St. Jude Children's Research Hospital junior faculty member; Thomas Look, MD, then chair of a St. Jude department; and their colleagues, who published the first of several reports detailing the discovery of ALK and the gene's pivotal role in ALCL. ALK is now widely recognized as a potent promoter of several adult and childhood cancers, including ALCL and neuroblastoma, a childhood tumor of certain nerve cells.

Hiroyuki Mano, MD, of the University of Tokyo, led the 2007 study that showed an ALK rearrangement as the driver of some NSCLC tumors. As a result, Pfizer expanded a phase 1 clinical trial of Xalkori to include patients with ALK-positive advanced NSCLC. Xalkori blocks the cancer-causing activity of the ALK protein. Additional clinical trials with the drug are now underway in other cancers, including neuroblastoma and ALCL, the lymphoma that launched the search.

This year about 210,000 new cases of lung cancer will be diagnosed in the United States. Current estimates are that approximately 3% to 5%, or 6,500 to 11,000 patients with NSCLC, carry the ALK rearrangement and may be candidates for treatment with crizotinib.

"We knew in 1994 when we initially discovered ALK that it was an outstanding drug-development target," said Dr Morris, who is now a member of the St. Jude Pathology and Oncology departments. "It is heartening to now see patients benefiting from our research."

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