The drug Gleevec (imatinib mesylate) is well known not only for its effectiveness against chronic myeloid leukemia (CML) and acute lymphoblastic leukemia, but also for the story behinds its development. The drug was specifically designed to target an abnormal molecule--a fusion of two normal cell proteins--that fueled a tumor's growth.
A similar drug might be able to tame some brain cancers, new research from Columbia University Medical Center has shown. A team led by Antonio Iavarone, MD, professor of neurology and of pathology and cell biology, Institute for Cancer Genetics, previously discovered that a fusion of two proteins (present only in cancer cells and different from the two in CML) drives some cases of glioma, a common form of brain cancer.
The team's most recent study, published in Clinical Cancer Research, looked closely at two patients affected by recurrent glioblastoma with the fused proteins, in a first in-human trial of a drug that targets half of the fusion protein. Those patients, the researchers found, responded particularly well to the drug, with clinical improvement and radiological tumor reduction. The responses lasted 115 and 134 days, respectively.
"This suggests that if we developed a drug that hits the fused protein more precisely, while leaving normal cells alone, we may get even better results," said Dr. Iavarone. "The real test of that will have to wait for the development of such a drug and the clinical trials."
The study also found the fused protein in a significant fraction of the 795 glioma cases they examined, indicating that a smart drug that targets the fused proteins could have a meaningful impact.
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The article is titled, "Detection, characterization and inhibition of FGFR-TACC fusions in IDH wild type glioma." The other contributors are: Anna Luisa Di Stefano, Marianne Labussiere, Karima Mokhtari, Yannick Marie, Aurelie Bruno, Blandine Boisselier, Marine Giry, Aurelie Kamoun, MarcSanson (Sorbonne Universités); Alessandra Fucci, Veronique Frattini, Pietro Zoppoli, Anna Lasorella (CUMC); Julien Savatovsky (Fondation Ophtalmologique A. de Rothschild); Mehdi Touat, Jean-Charles Soria (Gustave Roussy Cancer Center); Hayat Belaid, Ahmed Idbaih, Caroline Houillier (Groupe Hospitalier Pitié Salpêtrière); Feng R. Luo (Janssen Pharmaceutical); Josep Tabernero (Universitat Autònoma de Barcelona); Marica Eoli, Rosina Paterra, Gaetano Finocchiaro (Fondazione I.R.C.C.S Istituto Neurologico C. Besta);
Stephen Yip (University of British Columbia); Kevin Petrecca (McGill University); and Jennifer A. Chan (University of Calgary).
The authors declare no financial or other conflicts of interest.
The study was funded by grants from the National Cancer Institute (R01CA178546), National Institute of Neurological Disorders and Stroke (R01NS061776) and a grant from The Chemotherapy Foundation.
The Herbert Irving Comprehensive Cancer Center (HICCC) of Columbia University and NewYork-Presbyterian Hospital is dedicated to the cure of cancer through innovative basic, clinical, and population-based research and outstanding patient care. HICCC researchers and physicians are dedicated to understanding the biology of cancer and to applying that knowledge to the design of cancer therapies and prevention strategies that reduce its incidence and progression and improve the quality of the lives of those affected by cancer. Initially funded by the National Cancer Institute (NCI) in 1972 and designated comprehensive in 1979, the HICCC is one of 41 NCI-designated comprehensive cancer centers in the United States, of which only three are in New York State. The designation recognizes the Center's collaborative environment and expertise in harnessing translational research to bridge scientific discovery to clinical delivery, with the ultimate goal of successfully introducing novel diagnostic, therapeutic, and preventive approaches to cancer. For more information, visit http://www.
Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.
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