Developing Weapons Against Cancer

When Elwood Jensen won the Lasker Award for Basic Medical Research in October 2004, he was awarded what is commonly known as “America’s Nobel” for his work that has shaped cancer treatment and positioned the University of Chicago as a world leader in drug discovery.

Jensen, who is the Charles B. Huggins Distinguished Service Professor Emeritus in the Ben May Institute for Cancer Research at the University of Chicago, was a premier cancer scientist who made headlines for his discovery in the 1960s and 1970s that anti-estrogen drugs decreased breast cancer tumors. Each year, the lives of 100,000 women are saved as a direct result of his research.

Similarly, Janet Rowley, who received the Lasker in 1988 for discovering the genetic alterations that cause cancer in humans and that allow for cancer diagnosis in patients at the molecular level, was instrumental in the 2001 FDA approval of Gleevec, the first-ever targeted therapy to effectively zero in on a specific cause of cancer (in this case, a genetic abnormality linked to a rare form of leukemia, discovered by Rowley).

Behind both of these headlines is an intricate discovery process, led by Chicago scientists and involving a cadre of biomedical researchers, chemists, and clinicians whose collective and collaborative work are unveiling groundbreaking new paths for cancer treatment.

The University of Chicago’s preeminence in discoveries that improve cancer therapeutics is the result of an environment rich with the intellectual resources and clinical infrastructure to identify and test safer, more effective therapies for cancer. Chicago is working to build even more on this unique set of strengths. Specifically, the institution is enhancing opportunities for its top researchers and clinicians to work closely together, since it is just this kind of cross-collaboration that so often leads to breakthroughs.

One promising example is the collaboration between biochemist Geoffrey Greene and radiation oncologist Ralph Weichselbaum. Greene, who studies estrogen action, is building on pivotal discoveries by his Chicago mentors, Elwood Jensen and earlier works by Chicago Nobel Laureate Charles Huggins. Their findings had a direct and enduring impact on breast cancer treatment, and now Greene is finding ways to effectively employ estrogen therapy in a dual role, both therapeutic (for conditions like menopause, inflammatory bowel disease, and cancers of the breast and uterus) and prophylactic (protecting patients from breast and uterine cancer). Now he’s teaming with Weichselbaum to understand how radiation can be used more effectively to fight hormone-responsive cancers without drastic side effects on a woman’s healthy surrounding tissue.

At Chicago, strides in understanding the basic biology of cancer lead directly to new therapies. The University of Chicago is one of only five institutions nation-wide with the clinical infrastructure to support all three phases of clinical trials—Phase I, II, and III. Chicago’s seasoned clinical trial directors provide valuable partners for the National Cancer Institute and pharmaceutical companies, who provide expertise in trial design and execution, and help to uncover unexpected, promising results.

An example is Chicago’s Mark Ratain, who developed a novel clinical trial to test a new drug’s effectiveness against several types of tumors. Although the drug was first predicted to effectively fight colon cancer, Ratain’s trial also included patients with advanced renal cell cancer, 85 percent of whom do not respond to standard treatment. The results were unexpected: the trial revealed minimal effects on colon tumors, but caused dramatic and rapid shrinkage of renal tumors. Ratain is now advancing this trial to the next stage, and the outcome may provide greater hope to the more than 190,000 patients around the world affected by this disease.

In the age of the human genome, scientists at Chicago are leaders in another dimension of drug discovery. Beyond the clinical trial process, Ratain, along with Eileen Dolan and other Chicago cancer specialists, has spearheaded the rapidly-growing field of pharmacogenetics – the science of tailoring specific medications according to patients’ genetic make-up. Broadly applicable, pharmacogenetics is especially important for cancer patients, who undergo treatments that can cause debilitating and devastating reactions if the dosage is too high, or offer no benefit at all if the dosage is too low.

In both labs, Dolan and Ratain pinpoint the genes that cause toxic reactions to chemotherapy drugs. Ratain’s team then applies pharmacogenetics to patients. Most recently, they developed a simple blood test that can predict which colorectal cancer patients are likely to experience a harmful reaction to a common chemotherapy agent, irinotecan. With this unique new test, Ratain received worldwide acclaim for establishing a new stage of the therapeutic discovery process.

The University of Chicago’s cancer investigators receive over 40% of the government grants awarded to the Biological Sciences Division and Hospitals—a solid measure of the strength and promise of cancer research at Chicago. Seeking additional commitments from private philanthropists, Chicago will continue at the forefront of therapeutic discovery in cancer.

• A new research building to be completed in 2007 will provide state of the art laboratories for cancer research.
• New faculty will expand cancer treatment discoveries and facilitate the translation of these findings into improved outcomes for patients.
• New equipment, chemical libraries, and core facility development will enhance Chicago’s capabilities. Building a large and structurally diverse collection of natural and synthetic chemical compounds is essential. New drugs will be used to understand important cell signaling pathways and to manipulate these pathways to treat or prevent cancer.
• New programs for graduate and medical students to train in the field of pharmacogenetics and drug discovery will allow Chicago to develop more leaders in pharmacogenetics.

For more information about supporting the University of Chicago’s cancer research programs, please contact Stephanie Dahl at (773) 834-4726.

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