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School of Medicine
Promise and Progress - 1992-1996 The Abeloff Era: Building Upon a Tradition of Excellence
Special Commemorative Issue: The Abeloff Era - Building Upon a Tradition of Excellence
1992-1996 The Abeloff Era: Building Upon a Tradition of Excellence
Date: April 1, 2007
Led by new genetic discoveries and other pioneering cancer research, 1992-1996 were marked by tremendous growth. Ground was broken for the $125 million Harry & Jeanette Weinberg Building, bringing together all of the departments involved in treating cancer.
A Genetic Revolution
In his series of discoveries that helped identify cancer as a genetic disease, Bert Vogelstein is the first to identify the p53 gene as a tumor suppressor gene and link the mutation to the lethal progression of colon cancer. His discovery leads to findings revealing p53 as the most common mutation among cancers. In 1992, Time magazine recognizes Vogelstein’s work in its Best of Science issue. During this same time period, the Vogelstein/Kinzler laboratorycatapults gene testing into mainstream medicine with their discovery of hereditary mutations that predispose people to certain forms of colon cancer. Today, the tests they developed to identify these mutations are part of the routine management of patients with strong family histories of colon cancer and have dramatically altered how these patients are diagnosed and treated. As a result of these discoveries, Vogelstein’s investigations are seen as the benchmark for cancer research and biomedical research in general, and with more than 25,000 citations, he is named by Science Watch as the most often cited scientist in all of medicine.
Epigenetics—The Other Gene Alteration
Stephen Baylin leads a group of researchers who uncover a newway of altering cancer-related genes. Baylin’s pioneering work is part of a new field of cancer research called epigenetics. Epigenetic changes, like genetic ones, are found to pass from cell to cell as they divide but modify DNA without a mutation.The gene looks perfectly normal, but because the DNA has been rendered silent, it behaves like one that has undergone a cancer-causing mutation. The work centers on a cellular mishap know as DNA hypermethylation. Methylation is a normal cellular process, but Baylin and team find that when genes, such as tumor suppressors, receive too much methylation, they become invisible to cells. The researchers identify hypermethylation as one of the earliest alterations in cancer, making it a potential biomarker for early detection and diagnosis. Drugs that block methylation are seen as a potential new cancer therapy.
The National Cancer Institute introduces the SPORE (specializedprograms of research excellence) to speed the transfer of laboratory research to patient care. The Kimmel Cancer Center becomes the first Cancer Center to earn multiple SPORE grants. The first three grants are earned in lung, gastrointestinal, and prostate cancers. Today, the Center holds seven SPORE grants including breast, cervical, and head and neck cancers and lymphoma.
Capturing the Elusive Blood Stem Cell
Our blood is constantly changing, constantly renewing itself, churning out some 260 billion cells a day. Lost among this river of cells is the origin of this ongoing cycle and what could be the key to curing certain cancers, until Curt Civin figures out how to pull it out of hiding. Most investigators believe in the therapeutic potential of the hematopoietic stem cell, the cell that controls the type and number of blood cells produced in the body, but they considered isolating it a lost cause, like trying to find the proverbial needle in the haystack. Civin proves them wrong when he develops the CD34 antibody, and makes it possible for the first time to isolate and collect the vital stem cell. CD34 acts like a magnet attracting and separating blood stem cells from all other blood and immune cells. The clinical use of CD34 is approved by the FDA in 1996. Since then, it has been key to the treatment of more than 10,000 cancer patients worldwide and been the subject of thousands of scientific articles and investigations.
Awakening the Immune System
In 1989, when experts in the Cancer Center first begin investigating gene therapy and cancer vaccines, it seems there are more great minds working to disprove its potential than to prove it. Astonishing in its complexity and exquisite in its sensitivity, the human immune system is amazing at protecting our bodies from viruses and a host of foreign predators of all kinds— but not from cancer. Promising attempts to change this fact have failed and many are skeptical that the immune system can be manipulated to recognize cancer as a predator.
The tide turns, however, when the team of Drew Pardoll, Elizabeth Jaffee, and Hyam Levitsky devise a new approach. Instead of trying to fix the cancer cell, they decide to try to fix the immune system. The team inserts an immune-boosting gene into the nucleus of surgically removed human cancer cells, and when these genetically engineered cells are injected into mice, they awaken the dormant immune system and alert it to the presence of cancer cells, causing it to search out and destroy them. This groundbreaking work paves the way for some of the first therapeutic cancer vaccine trials in humans.Today, the Kimmel Cancer Center, has tested vaccines for kidney, prostate, cervical and pancreas cancers.
Bringing Cancer Cells Out of Hiding
Sidransky uses DNA replication errors called clonal markers to develop screening tests that detect small numbers of cancer cells in urine and other body fluids, tissues, and secretions at the very earliest stages and before they are detectable by pathology. The test is used to screen for bladder cancer and to help head and neck cancer surgeons differentiate normal tissue from normallooking cancerous tissue. The potential to test sputum and breast aspirate for traces of cancer cells is another application Sidransky is studying.
His first patient, however, is probably the most interesting, even though he is already dead. It was former vice president Hubert Humphrey, who died of bladder cancer in 1978. Though he seeks medical advice when he notices blood in his urine in 1967, former vice president Humphrey is never treated because the pathology at that time is inconclusive. In 1978, Humphrey dies of bladder cancer. Of course, this is years before Sidransky develops hisscreening test. Still, pathologist Ralph Hruban, who has obtained a sample of Humphrey’s tumor, is curious to see if Sidransky’s test can detect the cancer that classic pathology has missed.
Sidransky agrees and finds p53 gene mutations, a common fingerprint of bladder cancer, in the tumor and similar mutationsin 9 percent of the cells removed from Humphrey’s urine, proving that he had bladder cancer in 1967.
Continued work on these tests, Sidransky hopes, could one day lead to a broad-based screening test for cancer. “I envision a day,” he says, “ when people can go to see their doctors, provide urine, sputum or stool samples, and have them screened for bladder, lung and coloncancer.”
The Cancer Drug of the Decade
In the early 1990s, taxol is widely heralded as the best new anticancer drug to hit the market in decades. If not for the work of Ross Donehower, however, the drug likely will never make it to patients. Insoluble in humans, the drug, which is derived from the bark of the Pacific yew tree, is abandoned.Working with former Cancer Center investigator Eric Rowinsky, Donehower develops premedications that allows the drug to be tolerated by humans. The drug is now part of standard therapy for ovarian, breast, lung and other cancers.
A Cancer Center for the 21st Century
With more than 800 people on hand, ground is broken in 1994 for the $97.7 million Harry & Jeanette Weinberg Building. The building will become the largest facility on the East Baltimore campus and, for the first time in Cancer Center history, bring together in one ultramodern facility all the departments involved in treating cancer patients. Designed to be the most technologically advanced but with many patient and family friendly spaces, the 390,000-square-foot, six-floor facility will dramatically expand clinical space and increase patient comfort.Directly across from the Weinberg Building, research space will also be expanding with the construction of the $59 million, five-story, 217,000- square--foot Bunting Blaustein Cancer Research Building to house the state-of-the-art laboratories of some of the world’s leading cancer researchers. The new buildings will bring to fruition years of conceptualization and fund raising. They are the culmination of the visions of Drs. Albert Owens and Martin Abeloff, the Center’s first directors, to build on past successes and combine the best of both science and medicine into a truly comprehensive cancer center for the new millennium.
Shorter Hospital Stays for Bone Marrow Transplant Patients
The Center’s world famous Bone Marrow Transplant Program leads the way in moving cancer’s most intensive therapy to the outpatient clinic. The new program is called IPOP (for inpatient/outpatient). Bone marrow transplant involves using high doses of cancer drugs to destroy the diseased bone marrow of leukemia and certain other cancer patients.The cancer-filled bone marrow is replaced with healthy donor marrow that regrows, over time, forming new healthy immune and blood cells. However, while the bone marrow is repopulating, the patients are at high risk of life-threatening infection and bleeding. Patients are often hospitalized for 30 or more days. The IPOP program represents a collaboration between oncologists and nurses to closely monitor and manage side effects so that most patients can safely return home sooner.
Breast Cancer Survivors Fund Research
A dedicated group of cancer survivors and concerned Maryland women led by breast cancer survivor Harriet Legum raise $2.1 million for the first Breast Cancer Research Chair and Fellowship. Their goal is to support a talented senior faculty member while attracting and fostering bright young investigators. Nancy Davidson, director of the Cancer Center’s breast cancer program, is named recipient of the chair.