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tumor infiltrating lymphocytes armed with a gene that produces a potent antitumor agent, tumor necrosis factor, and this again is a result of the gene transfer technology that we were discussing.

Major progress has been made in reducing deaths from childhood cancers and in preventing or treating many common cancers in adults as well. However, there has been less progress in reducing the death rate from common solid tumors in patients age 65 and over. Many Americans, the poor, the underserved and members of some minority groups do not have access to state-of-the-art prevention, early diagnosis and treatment, and have disproportionately high cancer incidence and mortality rates. We must increase our efforts in cancer prevention and control.

Research on cancers that affect women is a high priority for the National Cancer Institute as cancer is the second leading cause of death among women in the United States with more than 150,000 women expected to die in 1991 of cancers of the lung, breast, colon, and reproductive tract.

NCI supported scientists are unraveling the genetic mysteries of the cancer cell and important new theories of how cancer evolves from the normal cell are emerging with increasing information about oncogenes and suppressor genes.

The NCI cancer centers program provides interdisciplinary cancer research and state-of-the-art diagnosis, treatment and rehabilitation, prevention, and cancer control, as well as community outreach and research on a number of cancers, including AIDS-related cancers, throughout the Nation.

Additionally, NCI's ability to transfer technology effectively rests on community programs such as the clinical cooperative groups and the community clinical oncology program which we refer to as our CCOP program. The latter are especially important in getting state-of-the-art treatment to rural areas, and we now have active participation in NCI funded clinical trials in many small towns throughout the country, some with wonderful names like Spirit Lake, Royal, and Rembrandt.

Among other new cancer drugs, there is a great interest in taxol as it can kill various cancer cells. This is an important drug. It is derived from the bark of yew trees and is in very short supply, but NCI is undertaking taxol development from alternative renewable resources. This is an important and, in fact, an emergency priority of the Institute.

Prevention is the most effective way to eliminate a disease, and NCI is studying smoking cessation, diet, chemoprevention, cancer vaccines, and the use of special hormones to prevent tumors.

The NCI has assisted in evaluating potential environmental issues such as those related to nuclear powerplant facilities.

The NCI also has an important mission in AIDS research, and works closely with other Federal agencies. While not the lead agency at the National Institutes of Health, the NCI is proud of its supporting role. NCI scientists have made vital contributions in areas such as basic biomedical research on the pathogenesis and natural history of the Human Immunodeficiency Virus (HIV]. We have drug development programs and vaccine development programs. The NCI intramural program is a leader in developing new therapies for children with AIDS and pediatric research in AIDS is an

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important priority of the institute. As people with AIDS are surviving longer, the incidence of AIDS related cancers is increasing, and NCI is working to meet this challenge.

PREPARED STATEMENT

One measure of the success of the National Cancer Act is that there are over 6 million survivors in the United States, people who have had cancer and who have survived. We have accrued a new understanding of the basic biology of cancer which in turn is pointing to effective prevention, diagnosis, and treatment. We must continue our progress, and the NCI stands to fulfill that goal.

Mr. Chairman, the 1992 budget request for the Institute totals $1,810,230,000.

I would be very pleased to answer any questions.
[The statement follows:]

STATEMENT OF DR. SAMUEL BRODER

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This year, the twentieth since the National Cancer Act was passed, has been marked by high scientific achievement for the National Cancer Program. Research on gene therapies is progressing, resulting in new ways of intervening against cancer. Studies assessing the cancer risk posed by nuclear facilities have been conducted. New drugs to treat cancer patients have been developed and new prevention strategies using vitamin derivatives have proven effective. A high level of sophistication in recombinant DNA technology has been achieved and much of the biotechnology industry in the United States has emerged from basic science investigations in these areas. One measure of the success of the National Cancer Act is that there are over six million cancer survivors in the United States today. Despite these and many other successes, the priority placed on cancer research by the National Cancer Act is as needed today as it was in 1971 when the National Cancer

Program was founded. There will be over a million new cases of cancer and a half million people will die of cancer in the United States this year. Many Americans who could benefit from the findings of this research do not currently have access to state-of-the-art prevention, early diagnosis and

treatment.

The National Cancer Institute also has an important role in AIDS research and works closely with the National Institute of Allergy and Infectious Diseases and other Federal agencies. NCI scientists have made vital contributions using basic biomedical research to study the pathogenesis and natural history of Human Immunodeficiency Virus (HIV) infection, AIDS drug development, and vaccine development. The NCI intramural program is one of the most important centers in the world for developing new therapies for children with AIDS. A new challenge is now on the horizon: as people with AIDS are surviving longer, the incidence of AIDS-related cancers is increasing, and NCI is working to meet this challenge.

Cancer is the second leading cause of death among women in the United States, with more than 150,000 women expected to die of lung, breast, and colon cancers and cancers of the reproductive tract in 1991. Women

participate in every phase of NCI research and NCI strives for proportional representation of women in all clinical trials. Research on cancers that affect the survival of women is an exceedingly high NCI priority.

Major progress has been made in reducing deaths from childhood cancers--a

reduction of 36 percent between 1973 and 1987. Almost two-thirds of children with cancer now survive to the 5-year "cure" point. There also has been important progress in preventing or treating many common cancers in adults as well, particularly in people under age 65 where, for instance, the death rate for colorectal cancer has fallen by approximately 15 percent in the last 20 years. The death rate for ovarian cancer has fallen by approximately 25 percent, about the same for stomach cancer, by 30 percent for bladder cancer, and by nearly 40 percent for cancer of the cervix.

There has been less progress in reducing the death rate from the common solid tumors in patients aged 65 and over. There are disproportionate rates of cancer mortality in some minority groups as well as in poor and underserved groups. Ironically, as technology for prevention, diagnosis and treatment improves, the groups without access to the technology appear to suffer even more. In recognition of this, NCI has begun and will continue in 1992 to develop new research and outreach programs to reach women, minority group members, older individuals and other underserved groups.

The NCI cancer centers provide a resource within their geographic area for interdisciplinary cancer research and for state-of-the-art diagnosis, treatment, rehabilitation, prevention and control of cancer. In 1992, the comprehensive cancer centers will continue to emphasize community service and outreach activities. In addition, the centers are emerging as a potent national resource for study of and state-of-the-art treatment for the rapidly increasing number of AIDS-related cancers as well.

NCI's ability to transfer technology effectively rests on programs such as the cancer centers, the Clinical Cooperative Groups and the Community Clinical Oncology Program (CCOP). The CCOP is a network of community cancer specialists, primary care physicians, and other health care professionals who conduct both clinical treatment research and cancer prevention and control research studies in the areas of early detection and screening, chemoprevention, smoking, patient management, continuing care, and rehabilitation. The current program involves over 300 hospitals and 2,100 physicians. Approximately 5,000 patients per year are entered onto treatment clinical trials through the CCOP alone, which represents about one-third of the annual Phase III accrual to NCI-approved randomized clinical trials.

New treatments continue to be developed. NCI scientists and colleagues from the National Heart, Lung and Blood Institute have conducted a number of

gene treatment studies. Last year, gene transfer research successfully traced the activity of reinfused genes. Last September, a related study introduced gene therapy for an extremely rare, inherited immune system disorder caused by the absence of the enzyme adenosine deaminase (ADA). The first patient, a 4year old girl, has received monthly transfusions of gene-corrected white blood cells, and preliminary results suggest that her immune function has improved. We are now at the point of inserting genes for specific tumor-fighting substances such as tumor necrosis factor into patients' genes. The first two patients were treated on January 29, 1991.

NCI-supported scientists are continuing to unravel the genetic mysteries of the cancer cell and as a result, important new theories of how cancer evolves from the normal cell are emerging. About 10 years ago it was discovered that a gene, located at the 13q14 position (on chromosome 13), was missing in familial retinoblastoma, a rare childhood cancer of the eye. The protein produced by the gene at 13q14 is called RB. The normal RB gene appears to play a role in the suppression of cancer.

Abnormalities in the RB

gene and the RB protein have been found in acute lymphocytic leukemia, osteosarcomas and in many of the common "adult" tumors such as lung and Abnormalities in another suppressor gene, p53, have been detected in colorectal cancer and other common malignancies, including lung and breast

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breast.

cancers.

The Li-Fraumeni syndrome is characterized by multiple tumors and is inherited within families. NCI-supported scientists have recently pinpointed

an inherited mutation of p53 as the responsible factor for these multiple Finding this critical gene may allow counseling of individuals with this inherited syndrome, and increase the understanding of the mechanisms that result in the transformation of a normal cell into a malignant cell.

NCI has an active drug development program for cancer and AIDS. NCI's high capacity drug screen examines synthetic compounds and natural products for activities against many human tumor cell lines and retroviruses such as HIV. A large number of the cancer drugs available today have been developed through the support of the National Cancer Program. Currently, there is great interest in the compound taxol as it can kill ovarian and breast cancer cells. Unfortunately, taxol is extracted from the bark of yew trees and stripping the However, so that clinical tests can go forward, NCI is making production of taxol from alternative renewable sources a priority. The

bark kills the tree.

tumors.

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