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More than $34 Million in SPORE Grants

Spurs research in leukemia, endometrial, pancreatic and lung cancers

Three new Specialized Programs of Research Excellence (SPORE) grants –– totaling $12.75 million for leukemia, $10.4 million for endometrial and $4.7 million for pancreatic cancer research –– have been awarded to the institution. M. D. Anderson also received $6.5 million in renewed funding for its lung cancer SPORE, first awarded in 1996. All four grants have been awarded to the institution in the last quarter.

With the addition of the new, five-year grants, M. D. Anderson now holds a total of eight NCI-sponsored SPOREs and ranks first in the number of grants received nationwide by the NCI.

M. D. Anderson's eight SPORE grants over the past seven years total more than $88 million. Before the new $6.5 million renewed award to M. D. Anderson, the grant for lung cancer research was originally given jointly to M. D. Anderson and the UT Southwestern Medical Center in Dallas in 1996. A second, $10 million SPORE grant for ovarian cancer research was awarded in 1999. In 2001, M. D. Anderson received both prostate and bladder SPORE grants, totaling $13.3 million and $13 million respectively –– making it the first institution to hold two such genitourinary cancer grants. A $12 million grant for head and neck cancer was awarded to the institution in 2002.

"We are grateful that M. D. Anderson has again been recognized by the NCI for its innovative and productive interdisciplinary research efforts," says John Mendelsohn, M.D., president of M. D. Anderson. "With these three new SPORE grants for leukemia, endometrial and pancreatic cancers, as well as renewed funding for our lung cancer SPORE, we will continue to build on our collaborative approach in the research and treatment of these diseases."

Federal funding plays an integral role in M. D. Anderson's success as a leader in translational research. In 2002, the institution spent more than $262 million for research –– an increase of more than 110 percent in the last six years. Of that $262 million, $118 million (45 percent) of M. D. Anderson's total research expenditures came from federally funded grants, such as SPOREs.

"Federal support is paramount to M. D. Anderson achieving its mission to eradicate cancer by funding the necessary infrastructure to sustain research in the laboratory, and by funding numerous research projects. Through our research, we are developing new approaches in clinical practice that we hope, in the near future, will greatly improve treatments impacting survival and quality of life for many patients with cancer," says Mendelsohn.

Monies from the highly competitive SPORE grants will fund research projects specific to each disease site, as well as establish a Career Development Program to train physicians and scientists, with a focus on translational research.

Since 1992, the NCI has awarded SPORE grants to certain cancer sites for concentrated research that focuses on projects with a translational emphasis.

SPORE Backgrounder

M. D. Anderson has received eight SPORE grants from the National Cancer Institute since 1996. Following is additional background regarding M. D. Anderson's leukemia, endometrial, pancreatic and lung cancer SPOREs and the corresponding disease site:

The Joe Moakley Research Excellence Program (Leukemia SPORE) According to the American Cancer Society, more than 30,600 new cases of leukemia will be diagnosed in 2003 and approximately 21,900 people will die of the disease. According to Hagop Kantarjian, M.D., professor and chair of M. D. Anderson's Leukemia Department and the SPORE's principal investigator, great strides have been made at M. D. Anderson and beyond in the treatment of several leukemia types, including chronic myelogenous leukemia (CML). In one of the fastest reviews ever conducted for a cancer therapy by the U.S. Food and Drug Administration (FDA), GleevecÔ was approved in May 2001 for the treatment of CML, and is the first in a new class of drugs known as protein kinase inhibitors that is designed to selectively inhibit an enzyme involved in the development of the disease. M. D. Anderson was a leader in clinical trials for this drug. Still, much more needs to be done to care for those individuals with other forms of leukemia, including acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), and myelodysplastic syndrome (MDS). Monies from the five-year, $12.75 million SPORE grant, the first ever SPORE to be funded for leukemia, will examine the genetics, biology, and markers unique to leukemias so new targeted therapies may be developed. Specifically, the SPORE will enable researchers to:

• understand the genetics of drug-resistant disease in AML, targeting hypermethylation-associated silencing of tumor suppressor genes
• identify target antigens for both graft versus leukemia effect (GVL) and graft versus host disease (GVHD), ultimately taking specific T cells for GVL and transferring those antigens to leukemia patients
• validate and implement a sequential blockade strategy that will diminish expression of BCR/ABL by developing therapeutic strategies to inhibit transcription of this oncoprotein
• investigate the role of PPARg – a nuclear transcription factor – its presence in leukemias, effect on apoptosis, and efficacy as a targeted therapy in conjunction with RXR
• examine epidemiologic risk factors associated with development of AML and the role that genetic susceptibility plays in the disease
• determine the efficacy of a FLT3 inhibitor, CEP-701, and to establish the optimal combination of chemotherapy to use in conjunction with FLT3 inhibitors in future clinical trials Jean-Pierre Issa, M.D., professor in the Department of Leukemia, serves as the grant's co-principal investigator.

Endometrial SPORE

According to the American Cancer Society, endometrial (also known as cancer of the uterus) cancer is the most common gynecologic cancer, with more than 40,100 women expected to be diagnosed with the disease in 2003. Despite the fact that endometrial cancer's incidence rate –– as well as its death rate –– is on the rise, research funding for uterine cancer trails behind that of both ovarian and cervical cancer, which, when combined, affect fewer women annually.

With M. D. Anderson's $10.4 million endometrial SPORE grant, the institution is the first to receive a SPORE for this disease type; it is also the first to hold two such distinguished grants for gynecologic oncology research.

M. D. Anderson received a $10 million SPORE grant in 1999 for the study of ovarian cancer.

The five-year endometrial SPORE will examine the relationship between obesity and the disease, new treatments, risk and biology of the disease. Specifically, it will:

• study a new selective estrogen-receptor modulator (SERM), compared to Megace for the treatment of women with endometrial adenocarcinoma in a Phase II trial
• determine if insulin resistance hyperinsulinemia associated with obesity increases estrogen-dependent proliferation in the endometrium and endometrial cancer risk, and then test in a chemoprevention trial whether pharmacologic interventions lower insulin resistance
• utilize DNA methylation profiling in a large group of Type 1 (less aggressive) endometrial cancers, Type 2 (more aggressive) endometrial cancers and women at risk for developing the disease
• examine gene expression in Type 1 and Type 2 endometrial cancers to quantify estrogen-dependent growth regulatory pathways

Thomas Burke, M.D., vice president and M. D. Anderson's chief medical officer and a gynecological oncologist, serves as principal investigator. Russell Broaddus, M.D., Ph.D., assistant professor in the Department of Pathology, and Karen Lu, M.D., assistant professor in the Department of Gynecologic Oncology, and George Stancel, Ph.D., of Dean of the Graduate School of Biomedical Sciences for The University of Texas Health Science Center at Houston will serve as co-principal investigators of the grant.

Pancreatic SPORE

Because pancreatic cancer accounts for only two percent of all newly diagnosed cancers in the United States each year, funding to the disease site, compared to others, has been slow. However, according to the American Cancer Society, pancreatic cancer will be responsible for approximately 30,000 deaths in the United States in 2003 –– making it the fourth leading cause of adult cancer deaths. The disease is often advanced by the time symptoms occur, says James Abbruzzese, M.D., professor and chair of M. D. Anderson's Department of Gastrointestinal Medical Oncology and the pancreatic SPORE's principal investigator. Only recently has the momentum for pancreatic research picked up steam –– with both dedicated federal and philanthropic funding increasing dramatically in the last year alone.

M. D. Anderson was one of three institutions recognized by the NCI with a SPORE as leaders in pancreatic cancer research. The University of Alabama and the Mayo Clinic both received a prestigious grant for this disease site.

M. D. Anderson's five-year, $4.7 million pancreatic SPORE will focus on identifying new targets for novel therapies and will investigate:

• development of novel gene therapy to specifically inhibit an important activating protein in pancreatic cancer, NF-kappaB, in hopes of leading to a direct therapeutic application for patients
• role of COX-2 over-expression in pancreatic cancer to determine if a combined inhibition of COX-2 and the signaling protein EGFR, may provide direction with respect to therapy for pancreatic cancer patients
• Sp-1, an important signaling protein, and its role for expression of multiple secondary proteins that contribute to aggressive behavior of pancreatic cancer
• effect of numerous chemical agents that are available to inhibit NF-kappaB signaling pathways to further the understanding of important growth promoting signaling pathways in pancreatic cancer
• variation of DNA repair capability among patients with pancreatic cancer, and determine if the ability to repair damage to DNA is a risk factor in the disease

Douglas Evans, M.D., professor in M. D. Anderson's Department of Surgical Oncology, and Mien-Chie Hung, Ph.D., professor and chair of the Department of Molecular and Cellular Oncology, are the grant's co-principal investigators.

Lung Cancer SPORE

M. D. Anderson received its first SPORE in 1996 when it was jointly awarded, with The University of Texas Southwestern Medical Center, a grant for lung cancer research. In order to decrease the incidence and mortality of lung cancer, both institutions have received $6.5 million in SPORE renewed funding. Lung cancer will be diagnosed in 171,900 Americans and 157,200 will die from in 2003, according to the American Cancer Society. The original SPORE awarded $5.6 million to both M. D. Anderson and The University of Texas Southwestern in 1996. The collaboration has produced several key findings including the identification of three lung cancer tumor suppressor genes on chromosome 3 that dramatically reduced human lung cancer growth in mice.

Projects to be continued or started include:

• translation of tumor suppressor genes into new therapeutics for lung cancer
• molecular epidemiology of lung cancer, comparing surrogate and target tissue markers
• apoptosis and invasion in genes in lung cancer
• P13K signaling pathway as a target for lung cancer prevention and therapy
• study of the drug Telomerase as a target for lung cancer therapeutics

John D. Minna, M.D., of The University of Texas Southwestern Medical School will again serve as the study's principal investigator while M. D. Anderson's Jack Roth, M.D., professor and chair of the Department of Thoracic and Cardiovascular Surgery, serves as the lung cancer SPORE's co-principal investigator.

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