05/01/2001 07:00:00

Caltech President Honored for Pioneering Work Leading to Cancer Therapy

PASADENA, Calif. — David Baltimore, the president of the California Institute of Technology, was one of five scientists to receive the 13th annual Warren Alpert Foundation Scientific Prize today, May 1, for research that ultimately led to a new groundbreaking cancer therapy.

The prize, awarded at a ceremony at Boston's Four Seasons Hotel, recognizes the significance of STI571, a new cancer therapy that has shown remarkable effectiveness against chronic myelogenous leukemia (CML) in clinical trials.

Created by understanding the fundamental mechanisms by which CML occurs, STI571 was cited by Dr. Francis Collins, director of the National Human Genome Research Institute, as an early example of the kind of rational drug design that will stem from human genome studies. At a recent lecture at Harvard Medical School he stated that the STI571 clinical trials have shown "pretty dramatic results and ones which we hope will be repeated in other disorders as we get this kind of molecular understanding of what's gone awry in disease."

Phase I clinical trials of STI571 have produced encouraging results for patients with CML, a form of cancer characterized by rising white blood cell counts. Currently approved treatments are aggressive and difficult for patients to tolerate. A person with CML, which affects an estimated 5,000 Americans each year, typically dies within five years. With STI571, however, clinical investigators report that so far, 51 of 53 patients who received the highest dose in one study have gone into remission with few and modest side effects.

In addition to serving as president of Caltech, Baltimore continues his work as a biology professor with an active research lab on campus. Baltimore and Owen N. Witte, MD, Howard Hughes Medical Institute investigator, and professor of microbiology, immunology and molecular genetics at UCLA and the Jonsson Cancer Center, were honored by the Alpert Foundation for the basic science investigations that characterized the genetic pathway to CML.

For their preclinical work that led to the creation of STI571, the Alpert Foundation presented the award to Alex Matter, MD, head of oncology research, Novartis Pharma AG, and Nicholas B. Lydon, PhD, formerly of Novartis and now vice president for small molecule drug discovery at Amgen, Inc. Brian J. Druker, MD, professor of medicine at Oregon Health Sciences University, was recognized for both his preclinical work and clinical trial investigations. The foundation will divide a $150,000 award among the winners.

CML is caused by a genetic anomaly triggered by the rearrangement of chromosomes nine and 22, forming what is called the Philadelphia chromosome. A molecular consequence of this anomalous chromosome is the Bcr-Abl gene, whose product is a member of the tyrosine kinase family of proteins, which play a central role in a variety of cellular processes. Bcr-Abl's cancer-causing properties were identified and characterized by Drs. Baltimore and Witte.

The presence of Bcr-Abl in 95 percent of CML patients made this molecule a particularly attractive target for the design of a selective kinase inhibitor. Matter, an early champion of kinase inhibitor research at Novartis, recruited Lydon to take on the effort of identifying Bcr-Abl inhibitors. Lydon, while working on this effort, began collaborating with Druker, whom he had met years earlier when Druker was an oncology fellow studying kinases in the 1980s at the Dana Farber Cancer Institute, a Harvard Medical School teaching affiliate. They ultimately identified STI571, and in 1998, after curing mice, the drug was taken into clinical trials, and today Druker continues to take a lead role in the development of STI571 for CML. The drug works by blocking Bcr-Abl's ability to transfer phosphate groups to acceptor proteins, a key process in signaling the continued growth of the tumor cells.

Recently, STI571 has also shown effectiveness against gastrointestinal stromal tumors (GISTs), which occur in an estimated 2,000 Americans each year. GISTs originate in the stomach or small intestine in cells that form the organs' connective tissue. Patients with malignant GISTs that cannot be removed by surgery generally die within a year or two of diagnosis. Researchers found that STI571 blocked another tyrosine kinase, KIT, the flawed protein found in GISTs, and one patient has shown significant shrinkage in tumor size.

The foundation's Scientific Advisory Committee comprises physicians and scientists from Harvard Medical School and the Massachusetts Institute of Technology and is chaired by Harvard Medical School dean Joseph B. Martin, MD, PhD. Each year the committee recognizes creative research that has dramatically affected the human condition.

Chelsea, Massachusetts, native Warren Alpert, chairman of Warren Equities, established the Alpert Prize in 1987 after reading an article about the University of Edinburgh's Kenneth Murray, who had developed a vaccine for hepatitis B. Alpert decided he would like to reward such far-reaching breakthroughs. He called Murray to tell him he had won a prize, then set about creating the foundation. To choose subsequent recipients, he asked Dr. Daniel Tosteson, then dean of Harvard Medical School, to convene a panel of experts to select and honor renowned scientists from around the world. Nominations are invited from scientific leaders nationwide.

In 1950, Warren Alpert, a first generation American, started his business with, as he tells it, $1,000 and a used car. Today Warren Equities and its subsidiaries, which market petroleum, food, and spirits and engage in transportation and real estate investments, generate approximately $900 million in annual volume and have more than 2,100 employees in 11 states. Forbes listed Warren Equities number 225 on its most recent list of the nation's largest privately held companies. Alpert is Warren Equities' sole owner and the foundation's sole benefactor.

Written by Jill Perry