Eli Canaani, Ph.D. performed molecular research leading to the development of Gleevec, the first drug to directly target cancer cells, now being used to treat Chronic Myelogenous Leukemia.
Born in Tiberius, Israel, Dr. Eli Canaani performs his research work at the Weizmann Institute of Science’s Department of Molecular Cell Biology, where he has been since 1981, after earning his doctorate at the University of California at Berkeley and performing postdoctoral work at the National Cancer Institute in Bethesda, Maryland. The ICRF has been supporting Dr. Canaani’s research work steadily since 1981.
Canaani’s early research focused on the molecular events that lead to the onset of Chronic Myelogenous Leukemia (or CML). That work helped pave the way for the development of the drug Gleevec, which targets cancer cells and is now routinely prescribed to patients with CML. It was later found that the molecular changes Canaani discovered – the exchange of portions of two chromosomes – are common in other types of leukemias, as well as in lymphomas, and soft tissue tumors.
“Many groups of researchers are now looking at genes directly involved in human cancer, but when our research began in the early 1980s, the field was relatively new,” he said. “The ICRF helped small groups, such as mine, make their mark.”
Together with Dr. Robert Gale, an American hematologist who spent a sabbatical in Canaani’s lab at Weizmann, they focused on a famous chromosome translocation termed the “Philadelphia Chromosome,” associated with CML. After much research, Canaani and his team were able to demonstrate that as a result of the exchange between chromosomes 9 and 22, two genes fuse and produce a leukemic fused protein. This was the first time that the making of a fusion protein was associated with a specific cancer.
The identification of the leukemic fusion protein triggering Chronic Myelogenous Leukemia prompted research groups in universities and in industry to study the protein biochemically, and attempts were made to devise a drug that would inhibit it specifically. This “rational therapy” approach led to the development of the drug Gleevec, which made international headlines when it was approved by the Food and Drug Administration in 2001.
“Gleevec is probably the most striking example of a new class of anti-cancer drugs based on the identification of a protein that triggers a specific cancer, and which is designed to inhibit this protein,” Canaani said. In addition to CML, Gleevec, made by Novartis AG, has also been approved for use in controlling a type of stomach cancer called GIST, and several other diseases. By 2011, Gleevec has been FDA approved to treat ten different cancers. An international analysis of patients with CML, for which Gleevec was originally designed, reportedly found that 89 percent of patients who have been taking the drug daily for five years are still alive and well today.
Though not directly involved with the development of Gleevec, Canaani said he is satisfied that the “the drug is based on fundamental insights into the origin of the disease provided by my work and that of several other scientists.” “It doesn’t happen very often that you see your research come to fruition – where a drug is developed as a direct result of your past work. It is very gratifying but, more importantly for me, those in the field know by whom the original research was done,” he said.
Regarding his research today, Canaani, the father of two (both of whom are entering different fields of medicine), said he had been working for the past dozen years on finding a cure for two types of leukemia: infant acute leukemia and acute leukemia triggered by anti-cancer treatment. These also involve chromosome translocations.
“We know the initial molecular events leading to the aforementioned leukemias, but we now focus on identifying proteins acting at later stages,” he said. “The hope is that once such a protein is identified, a specific drug, like Gleevec, could be devised to repress the protein and halt the disease.”