When President Nixon signed the National Cancer Act 40 years ago, the prognosis for people with chronic myeloid leukemia (CML) was grim. The only treatment was busulfan, says Brian Druker of the Oregon Health and Science University Knight Cancer Institute. “This chemotherapy drug did virtually nothing to improve survival, which at that time was no more than 3 to 5 years.”

But a 1996 paper by Druker and colleagues gave patients a reason to hope (Nat Med 1996;2:561–66). Knowing that patients with CML harbor a chromosome translocation that creates the mutant gene BCR-ABL, researchers tested a kinase inhibitor dubbed STI571, which targets BCR-ABL activity. When they added the compound to CML cells in a Petri dish, the cells died overnight. Later, when mice implanted with CML cells were given the agent, their tumors regressed. STI571 even killed leukemia cells in samples of patients' bone marrow.

Druker's team launched a phase I clinical trial of STI571, or imatinib (Gleevec; Novartis). The results, reported in 2001, were dramatic: Of the 54 patients who received daily doses of at least 300 mg, 53 had normal blood counts within a month. Food and Drug Administration approval for imatinib quickly followed.

That triumph spurred the development of additional targeted therapies, including a few to combat CML in patients who relapse while taking imatinib. Japanese investigators showed that KIT mutations are present in most patients with gastrointestinal stromal tumor (GIST) and that imatinib inhibits KIT. Fine-tuning of drug regimens for these diseases continues. In June, for example, researchers reported that GIST patients could significantly delay the disease's recurrence and prolong their survival by taking imatinib for 3 years after surgery instead of 1 year, the current standard.

“Only after we knew imatinib worked, did we realize how the approach might be generalized to other cancers with driver mutations,” says Memorial Sloan-Kettering's Charles Sawyers, who worked with Druker. “GIST was serendipitous.”

This article is the first in a 5-part series commemorating the passage of the National Cancer Act in 1971.