A drug recently approved by the U.S. Food and Drug Administration for treatment of an adult cancer targets a malfunctioning gene discovered more than a decade earlier at St. Jude Children’s Research Hospital. The story highlights how scientific findings from St. Jude can be translated into therapies and tests that in addition to helping children, also help adults.
The drug is Xalkori (crizotinib). The FDA approved Xalkori in August as the first targeted therapy for patients with ALK-positive non-small cell lung cancer (NSCLC) that is locally advanced or metastatic. Xalkori is manufactured by the pharmaceutical company Pfizer.
The ALK gene was discovered by St. Jude scientists searching for genes affected by a chromosomal change common in the cancer cells of patients with anaplastic large cell lymphoma (ALCL).The blood cancer accounts for 10 to 30 percent of pediatric non-Hodgkin lymphoma. In 1994 Stephan Morris, M.D., then a St. Jude junior faculty member; Thomas Look, M.D., then chair of a St. Jude department; and their colleagues, published the first of several reports detailing the discovery of ALK and the gene’s pivotal role in driving the cancer. ALK is short for anaplastic lymphoma kinase, the name investigators gave the protein whose assembly instructions the gene carried.
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. The work done by Morris, Look and their colleagues in a fifth-floor laboratory of the Danny Thomas Research Center eventually helped to launch a new targeted cancer treatment.
Hiroyuki Mano, M.D., of the University of Tokyo, led the 2007 research into the molecular drivers of NSCLC. The study showed some NSCLC tumors were driven by an ALK rearrangement. Following this discovery, Pfizer expanded a Phase I 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.
The ALK discovery and related later research led to five U.S. patents for St. Jude. The patented work includes methods for detecting the chromosomal rearrangements that unleash the cancer-causing ability of the ALK gene as well as tools to identify and characterize drugs for cancers caused by ALK deregulation. Morris, Look and their colleagues also worked with another pharmaceutical company to design a diagnostic assay to identify patients with the ALK mutation. The test, a fluorescence in situ hybridization (FISH) assay, has been marketed for more than a decade. In August, it won FDA approval as a diagnostic test for use with Xalkori.
Dr. William E. Evans, St. Jude director and chief executive officer, said the ALK story captures an important aspect of the hospital’s commitment. “Our focus is on finding cures for pediatric diseases, but our discoveries often provide insights that can be building blocks for advances in other diseases, including adult cancers. We are committed to facilitating this so that the most good can come from our discoveries,” he said.
Working through the St. Jude Office of Technology Licensing, Pfizer obtained licenses to the hospital’s patented research tools. Several other companies have executed licenses with St. Jude to use these patent rights.
This year about 210,000 new cases of lung cancer will be diagnosed in the U.S. Current estimates are that approximately 3 to 5 percent, or 6,500 to 11,000 patients with non-small cell lung cancer, carry the ALK rearrangement and may be candidates for treatment with Xalkori.
Today, Morris is a member of the St. Jude Pathology and Oncology departments. Look is a professor of pediatrics at Harvard Medical School and the Dana-Farber Cancer Center in Boston. Morris is still asking questions about ALK, including the protein’s normal functions. He said he is thrilled that his work offers new hope for thousands of lung cancer patients. “We knew in 1994 when we initially discovered ALK that it was an outstanding drug-development target,” Morris said. “It is heartening to now see patients benefiting from our research.”
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20 percent to 80 percent since the hospital opened more than 50 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food — because all a family should worry about is helping their child live. To learn more, visit stjude.org or follow St. Jude on social media at @stjuderesearch.