According to Charles J. Sherr, a Howard Hughes Medical Institute researcher at the St. Jude Children's Research Hospital in Memphis, Tennessee, his team's new findings may help doctors understand why some cancers can be controlled with drugs, at least temporarily, while others somehow resist treatment.
Sherr and colleagues Richard T. Williams, the lead author, and Martine F. Roussel reported their research findings on April 17, 2006, in an advance online publication in the Proceedings of the National Academy of Sciences.
The investigators studied two types of leukemia: CML chronic myelogenous leukemia, which can now be alleviated to a large extent with a drug called Gleevec (imatinib), and a subtype of ALL acute lymphoblastic leukemia, which does not respond well to this drug. The hallmark of both diseases is a genetic alteration in an enzyme (BCR-ABL) whose activity is specifically blocked by Gleevec treatment. The work reveals that loss of a gene known as Arf, which is frequently mutated in patients with ALL, but not CML, can cause some leukemias to resist Gleevec treatment.
Patients with CML who are taking Gleevec readily go into remission, and their cancer cells stop growing while they are maintained on drug therapy. Sherr explained that Gleevec's impact has been truly revolutionary. "It's a targeted therapy that works; the results have been miraculous."
Unfortunately, there is still a small relapse rate about five percent per year that doctors would like to erase. Other researchers have found that "patients who fail while on therapy have developed subsequent mutations in the BCR-ABL enzyme" that alter Gleevec's effectiveness," Sherr said.