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Significant Accomplishments and Discoveries

Faculty and staff involved in cancer research at the University of Wisconsin Carbone Cancer CenterUW Carbone Cancer Center (UWCCC) have been at the forefront of cancer treatment and research, participating in many "firsts" for the national and international cancer community.

1930s

 

Frederick Mohs, MD develops a surgical technique to remove external tumors such as mouth, lip and skin cancer. Mohs Micrographic Surgery relies on careful small dissections instead of the gross removal of tissue, allowing surgeons to work precisely, sparing normal tissue.

 

The UW's first formal foray into cancer research came in 1936 when the University sponsors a conference of American and European investigators.

 

In 1939, Harold Rusch, MD shows that a high-fat or high-calorie diet accelerates the production of cancer in mice.

 

1940s

Harold Rusch identifies the wavelength of ultraviolet light that causes skin cancer.

 

At the UW-Madison, the McArdle Laboratory for Cancer Research is established as the first basic science cancer center at an academic institution in the United States and one of the first in the world. Harold Rusch, MD serves as Director.

The McArdle Laboratory for Cancer Research receives its first multi-investigator National Cancer Institute block grant in 1946 and has 54 years of continuous support as a basic science cancer center until consolidation with the UWCCC in 2000.

UW and it's medical school grants departmental status to the McArdle faculty thus forming the Department of Oncology in 1947.

1950s

 

Van R. Potter, PhD develops the concept that laid the foundation for combination drug therapy, now the most widely used form of drug treatment for cancer. Potter theorizes that administering several drugs, chosen according to the area of the cell they affect, could be more effective than single-drug therapy.

 

Studies by Roswell Boutwell, PhD shed light on the mechanisms by which control of caloric intake protects against cancer, especially breast cancer. Boutwell is one of the first to propose that vitamin A plays a role in preventing cancer, a concept since validated in clinical trials using a vitamin A derivative.

 

The right to grant advanced MS and PhD degrees in Experimental Oncology is awarded by the UW and medical school. To date, more than 1500 graduate students and postdoctoral fellows have come through the program. 

Charles Heidelberger, PhD receives a patent for the design and synthesizes the drug fluorouracil, also known as 5-FU. Fred Ansfield, MD conducts the first human clinical trials using 5-fluorouracil and confirms the importance of constant exposure to 5-FU for a therapeutic effect. Cancers of the breast, colon or rectum, stomach, cervix, ovary and malignant hepatomas are found to be responsive to 5-FU.

 

1960s

Elizabeth Miller, PhD and James Miller, PhD markedly advance our understanding of how certain chemicals cause malignancy. In the 1950s and '60s, the Millers find that many known carcinogens must be "activated" in the body to initiate cancer.

 

The American Society of Clinical Oncology (ASCO), the leading professional organization representing all oncology disciplines and sub-specialities whose mission is to improve cancer care and prevention, is established by Fred Ansfield, MD and colleagues.

 

The research and advice of Derek Cripps, MD, PhD lays the foundation for the US Food and Drug Administration adoption of the sun protection factor (SPF) ratings, now found on suntan and cosmetic products.

 

Fritz Bach, MD develops the mixed leukocyte culture (MLC) test which is instrumental in identifying siblings as potential bone marrow donors. Two years later, Bach's team and one from the University of Minnesota uses this information to simultaneously perform the world's first successful allogeneic, or sibling-to-sibling, bone marrow transplants.

 

George Bryan, MD, PhD finds evidence linking cancer in laboratory animals with saccharine and cyclamates, artificial sweeteners used in soft drinks and other foods.

 

In the 1960s and 70s McArdle's director Henry Pitot, MD, PhD demonstrates that the environmental regulation of gene expression in primary and transplanted hepatocellular cancers is defective and significantly different from that in normal livers.

 

1970s

 

Howard Temin, PhD discovers reverse transcriptase (independently discovered by David Baltimore and Renato Dulbecco) and its role in the life cycle of retroviruses, for which he is awarded the Nobel Prize in 1975 with Baltimore and Dulbecco. Their discovery would go on to explain how retroviruses cause cancer and AIDS. 

Harold Rusch is appointed to the National Panel of Consultants on the Conquest of Cancer (known as the Senator Yarborough Committee). The report of this distinguished committee forms the basis for the Bill that President Nixon signed into law creating the National Cancer Act. Among a number of new initiatives to support a greater effort to conquer cancer is the authorization to establish fifteen new comprehensive cancer centers.

Henry Pitot accepts the Director of the McArdle Laboratory for Cancer Research.

 

The University of Wisconsin Clinical Cancer Center is established as one of six new comprehensive cancer centers by the National Cancer Institute, the lead federal agency for cancer research, in 1973. Harold Rusch is named UWCCC Director.

 

The UW Clinical Cancer Center sponsors the nation's first telephone-based cancer helpline (800-4-CANCER) as part of the National Cancer Institutes Cancer Information Service.

The University and Medical School's academic Department of Human Oncology is established as the nucleus of UWCCC. Harold Rusch becomes the first Chair of the Department in 1975.

Paul Carbone, MD succeeds Harold Rusch as Chair of the Department of Human Oncology in 1977 and serves as Director of the UWCCC from 1978-1997. 

 

In the 1970s and 80s, Douglas Tormey, MD, PhD explores the use of the anti-estrogen drug tamoxifen to decrease the chances of breast cancer recurring. Tormey's findings drew upon research begun in the 1970s by V. Craig Jordan, PhD. In May, 1997, the National Cancer Institute announced the recruitment of the 13,000th and final woman to a key national study based upon these findings.

 

Paul Carbone serves as Chair of the Eastern Cooperative Oncology Group and with the help of key UWCCC members had a great deal of influence on national clinical trials including studies involving adjuvant therapy for the treatment of breast cancer using tamoxifen and chemotherapy after surgery.

 

1980s

  

Researchers led by the Ernest Bordan, MD perform the first clinical trials using two types of interferon produced by recombinant DNA. Interferon is a natural substance that helps stimulate the body's defense mechanism to fight cancer.

 

Bill Sugden, PhD discovers the mechanism by which the cancer-causing Epstein-Barr virus grows in infected human cells.

 

In the 1980s and 90s, William Dove, PhD and Amy R. Moser, PhD isolate the mutant MIN mouse, the first animal model for familial colon cancer.

 

Donald Trump, MD conducts one of the first studies determining the safest, most effective dosage of taxol, a cancer fighting drug derived from the bark of Pacific yew trees.

 

Richard Love, MD, directs the first study in the US to determine the long term effects of tamoxifen on postmenopausal women who have had cancer.

 

Paul Sondel, MD, PhD leads a team conducting the first study on the safest, most effective dosages of interleukin-2, a natural substance that bolsters the body's immune system.

 

Between 1986 and 1996, Edward Messing, MD is the first to document that home screening for blood in the urine is a feasible way to detect early stage urologic malignancies.

 

Catherine Reznikoff, PhD transforms commonly-found human cells into an immortal, cancer-like growth in the laboratory.

 

Waclaw Szybalski, PhD, in conjunction with a Polish scientist discovers "chemical scissors" to allow researchers to cut DNA at specifically chosen sites. This is the first tool with precise capability; previous genetic slicers could locate and cut only a limited number of sites.

 

In 1986, the nation's first voluntary state-based effort to overcome barriers to adequate pain management is founded by June Dahl, PhD. The Wisconsin Cancer Pain Initiative provides a model and technical assistance for initiatives in all 50 states.

 

UWCCC begins regional cancer affiliates with hospitals throughout Wisconsin.

1990s

In the 1980s and 90s, F. Michael Hoffmann, PhD and colleagues use fruit fly genetics to identify two novel pathways that intersect with the Abl gene, a common target in leukemia.

 

In 1991 Norman Drinkwater, PhD succeeds Henry Pitot as the third Chair of Oncology and Director of the McArdle Laboratory for Cancer Research.

 

In 1991 David DeMets, PhD becomes Chair of the new Biostatistics department and develops a program heavily focused on cancer research.


Following more than 20 years of research into the carcinogen dioxin, Alan Poland, PhD and his team clone the cDNA for a soluble cellular protein, Ah receptor, that binds and transports dioxin and like-acting carcinogens. The research provides new clues to the mechanisms of dioxin's effects on the cell.

 

H. Ian Robins, MD, PhD successfully combines chemotherapy and systemic hyperthermia in a way that increases effectiveness without increasing side effects.

 

Judith Stitt, MD and Dolores Buchler, MD describe the results of high dose rate brachytherapy for the treatment of cervical cancer with outpatient radiation therapy.

 

Jeffrey Ross, PhD isolates and characterizes the first enzyme that regulates the stability of messenger RNA.

 

Richard Burgess, PhD discovers a new class of monoclonal antibodies, called polyol-responsive, that are ideal for rapid, gentle purification of unstable cellular proteins.

 

Norman Drinkwater, PhD and his students identify three genes that determine the risk of developing liver cancer among inbred mice. Thee genes may serve as a model for inherited factors that influence human cancer risk.

 

Researchers led by David Mahvi, MD launch the world's first test of "gene gun" technology in cancer patients. The therapy uses a gun-like device to "shoot" new genetic commands into cells from a patient's tumor in attempt to coax white blood cells from the patient into producing an immune response powerful enough to stifle cancer.

 

In 1994, UW-Madison decides to consolidate its two outstanding cancer centers: UW Comprehensive Cancer Center and McArdle Laboratory for Cancer Research.


John Niederhuber, MD serves as Director of the UW Comprehensive Cancer Center (UWCCC) from 1997-2002. Among his major accomplishments was the merger of the UWCCC with the McArdle Laboratory for Cancer Research - forming eight research programs. These research programs optimize intra- and inter-programmatic research and facilitate efforts to apply discoveries to improving the care of our cancer patients.

Dr. Niederhuber went on to become the Chair of the National Cancer Advisory Board, National Cancer Institute's Deputy Director for Translational and Clinical Sciences and Director of the National Cancer Institute.

The Wisconsin Oncology Network is established to include community hospitals in UWCCC clinical trials.

2000s

UWCCC successfully competed for many multi-investigator grants including a National Cooperative Drug Discovery Group in Cancer; a planning grant to develop an Aging and Cancer Program; establishment of a Center of Excellence in Cancer Communication Research; coordination of a Biochemical Prevention Clinical Trial Network; an O'Brien Center grant to study Prostate Growth Regulation; a Transdisciplinary Tobacco Use Research Center; a Bioengineering Research Partnership for the Biomolecular Analysis of Liquid Crystals; and a DOD Prostate Cancer Research Program Clinical Consortium award.

 

Tomotherapy is first used to treat patients in 2003. Developed by Thomas R. Mackie, PhD and Minesh Mehta, MD, a tomotherapy machine combines two devices into one that, with the help of complex software, seamlessly detects and defines cancer tumors, then delivers appropriate doses of radiation.

 

Peggy Farnham, PhD and her students isolate two genes (CRG-LI  and CRG-L2) that could lead to a simple test indicating the presence of liver cancer long before patients currently begin noticing symptoms.


George Wilding, MD is named Interim Director in 2002 and Director of UWCCC from 2004-2013. Wilding is instrumental in moving UWCCC toward a direction emphasizing multidisciplinary and trans-disciplinary interactions, focusing on the translation of basic research findings to clinical testing and application.

 

UW-Madison receives a $10 million grant to fund NCI's Center of Excellence in Cancer Communications Research, led by David Gustafson, PhD. The grant strives to improve the quality of life for cancer patients and their families, particularly those from underserved populations.

 

UWCCC is selected by the National Institutes of Health as one of eight research centers to study the relationship between cancer and aging.

 

Jamey Weichert, PhD develops a radioactive imaging agent - NM404- that has the potential to more accurately locate and define tumors in human patients.  Weichert has confirmed that NM404 is selectively retained in 14 different animal tumor models.

 

UWCCC receives a $7 million construction grant for new breast cancer research space. The grant is composed of $4 million from the National Center for Cancer Resources and $3 million from the National Cancer Institute. The funding houses interdisciplinary breast cancer research on one of four new Cancer Center floors in the Wisconsin Institutes for Medical Research.

 

Gelsomina De Stasio, PhD and her team develop a new radiotherapy technique for fighting glioblastoma multiforme (GBM) using gadolinium. Gadolinium Synchrotron Stereotactic Radiotherapy (GdSSR) relies on a gadolinium compound to find tumor cells and penetrate them into their nuclei while sparing normal brain cells.

 

Michael Gould, PhD and his team discovers genetic variations on regions of the human genome that significantly associate with breast cancer risk in women. Unlike current genetic strategies for assessing breast cancer risk, which involve looking for mutations of BRCA1 and BRCA2, Gould's research identifies risk associates with areas of the genome that harbor so-called modifier genes that do not make proteins but instead act to influence other genes elsewhere on the genome and that help initiate the cascade of events that leads to breast cancer.


Ground is broken on UW School of Medicine and Public Health's Interdisciplinary Research Complex (IRC) in 2005. The IRC will prominently feature translational cancer research at the UWCCC. The IRC is subsequently named the Wisconsin Institutes for Medical Research (WIMR) and opens in 2008.

The Cancer Center is renamed the UW Carbone Cancer Center in 2006, recognizing the contributions of former UWCCC director Paul Carbone who came to Wisconsin in 1976 and led the cancer center for 18 years. The Cancer Center's central research tower is named the Harold P. Rusch Translational Research Tower.

 

UWCCC plays an important role in getting a bill passed in the Wisconsin Legislature which Governor Jim Doyle signed in March 2006, requiring insurance companies to pay for routine care costs associated with cancer clinical trials.

 

Vladimir Spiegelman, MD, PhD and his team discover that messenger RNA bound by CRD-BP, a protein activated in colorectal and other cancers, prevents degradation and thus becomes - in this case, a full-fledged cancer-causing oncogene.

 

Paul Lambert, PhD and his team test two breast cancer drugs: fulvestrant and raloxifene, when tested on HPV-positive mice with cervical cancer. One month later all signs of cancer are gone.

 

Halcyon Skinner, PhD, MPH and researchers at Wake Forest University School of Medicine discover that some elevated prostate-specific antigen (PSA) levels in men are caused by parathyroid hormone, a substance the body produces to regulate calcium in the blood. The finding is especially significant for black men since about 20 percent of black men have elevated parathyroid hormone levels as compared with 10 percent for white men. This means that blacks have twice the risk of being recommended for unneeded biopsy and treatment.

 

2010s 

 

Shannon C. Kenney, MD finds that in mice, Hsp90 (heat shock protein 90) inhibitors prevent EBV-induced tumor cells from growing, protect immune cells from transforming into tumors and kill established tumor cells at low, non-toxic doses.

 

Research led by Amy Trentham-Dietz, PhD and Polly Newcomb, PhD find that lobular breast cancer is more closely associated with obese women who have never had children or those who waited until 30 or later to have a baby.  While other studies have linked later childbirth to an increased chance of lobular breast cancer, Trentham-Dietz's and Newcomb's study is the largest in the US that finds the association and to observe its increased effect with obesity.

 

Igor Slukvin, PhD, MD and his team successfully reprogram blood cells obtained from a patient with chronic myeloid leukemia back into pluripotent stem cells. The induced stem cells generated from the diseased tissue retain the exact same complex of genetic abnormalities found in the mature cancer cells. That means that when the induced cells are turned back to blood, scientists could, in theory, watch cancer develop from scratch as cells bearing cancer mutations become cancer stem cells.

 

Shigeki Miyamoto, PhD and colleagues develop a strategy that keeps the gene-regulating protein NF-κB from leaving the cell nucleus which is necessary for the formation of healthy B cells. This strategy could be used to stop NF-κB abnormalities that are known to cause B-cell cancers such as lymphomas and myelomas.

 

Patricia Keely, PhD analyzes 200 biopsy samples of breast cancer tissues and finds that straight 'highways' of collagen fibers shooting through connective tissue perpendicularly from tumors are associated with poor patient outcomes. Tumor associated collagen signatures or TACS are arrangements of collagen that change as cancer progresses to different stages. Keely expects that the TACS analysis of connective tissue may also be useful for other kinds of cancers, including colon, ovarian and some kinds of skin cancer.

 

Researchers in the laboratory of Emery Bresnick, PhD find two proteins, ETO-2 and LMO2, in a multi-protein complex that act independently and exert very different functions. The discovery was entirely unexpected and has implications not only for understanding how the complexes work but how different cancers can arise when different proteins are dysregulated.

 

Completion of WIMR Tower II in 2013 will result in the move of the Department of Oncology, including the McArdle Laboratory for Cancer Research, to WIMR and successfully achieve a tripling of UWCCC clinical and research space since 2002.

 

Howard Bailey, MD is named UWCCC Interim Director, effective September 1, 2013. Dr. Bailey, a Professor of Medicine, is a Medical Oncologist specializing in Gynecologic Oncology and Cancer Prevention. A national search begins in the Fall 2013 to find a permanent director.