Current National Cancer Institute Research Articles

Updating the Definition of Cancer.

Most definitions of cancer broadly conform to the current NCI definition: "Cancer is a disease in which some of the body's cells grow uncontrollably and spread to other parts of the body." These definitions tend to describe what cancer "looks like" or "does" but do not describe what cancer "is" or "has become." While reflecting past insights, current definitions have not kept pace with the understanding that the cancer cell is itself transformed and evolving. We propose a revised definition of cancer: Cancer is a disease of uncontrolled proliferation by transformed cells subject to evolution by natural selection. We believe this definition captures the essence of the majority of previous and current definitions. To the simplest definition of cancer as a disease of uncontrolled proliferation of cells, our definition adds in the adjective "transformed" to capture the many tumorigenic processes that cancer cells adopt to metastasize. To the concept of uncontrolled proliferation of transformed cells, our proposed definition then adds "subject to evolution by natural selection." The subject to evolution by natural selection modernizes the definition to include the genetic and epigenetic changes that accumulate within a population of cancer cells that lead to the lethal phenotype. Cancer is a disease of uncontrolled proliferation by transformed cells subject to evolution by natural selection.

The Emperor of All Maladies

The Emperor of All Maladies

Ethnobotany and drug discovery: the experience of the US National Cancer Institute.

Between 1960 and 1981 the National Cancer Institute (NCI) screened 114,000 extracts of 35,000 plants, mainly collected in temperate regions. Of the three clinically active anticancer drugs so far discovered in that programme, none was isolated from a plant collected on an ethnobotanical basis, though various Taxus species, which are the source of taxol, are reported to have been used medicinally. Since 1986, the NCI has focused its collections in tropical and subtropical regions worldwide; collections cover a broad taxonomic range, though priority is given to medicinal plants when relevant information is available. As of August 1993, 21,881 extracts derived from over 10,500 samples had been tested in a screen for activity against the human immunodeficiency virus (HIV); 2320 of these extracts were of medicinal plant origin. Approximately 18% of both the total number of extracts and the medicinal plant-derived extracts showed significant anti-HIV activity; in each instance about 90% of the active extracts were aqueous. The activity of the aqueous extracts has been attributed mainly to the presence of polysaccharides or tannins. Four plant-derived compounds are in preclinical development at the NCI; only one of the four sources plants, obtained from a noncontract source, was collected on an ethnobotanical basis. At this stage the results indicate that the current NCI collection policy offers the best chances for the discovery and development of agents for the treatment of AIDS (acquired immune deficiency syndrome) and cancer.

The Racial Disparity Gap in Pediatric Leukemia and Lymphoma Survival Has Been Eliminated in Children but Not in Older Adolescents and Young Adults.

Overcoming disparities in the successful treatment of minority cancer patients has been a major challenge. In particular, blacks/African Americans face a higher likelihood of developing and dying from each of the four most common malignancies in the United States (breast, prostate, colon, and lung cancer) as well as from other cancers. Among children, leukemia and lymphoma have also shown a worse outcome in black patients versus whites. Given the success of the Children's Oncology Group (COG) in reducing the racial deficit in leukemia and lymphoma, we examined national survival data from the U.S. Surveillance, Epidemiology and End Results (SEER) program for trends in survival difference between white and blacks with leukemia and lymphoma, as a function of age at diagnosis. The annual 5-year relative survival rate trends during 1975 to 2000 for all leukemia and all lymphoma (including Hodgkin lymphoma) showed convergence in white and black children (age <10), comparable trends in 10- to 19-year-olds, and divergence in those 20 to 29 years of age with blacks doing progressively worse than whites. The age dependent patterns were qualitatively similar for acute lymphoblastic leukemia, acute myelogenous leukemia, and non-Hodgkin lymphoma, with convergence in <10 year-olds and divergence in 20- to 29-year-olds apparent in each type of leukemia and lymphoma. For the year 2000, the trends in 20- to 29-year-olds project a 20 to 25% survival deficit for blacks versus whites for acute myelogenous leukemia and a 5 to 10% deficit for other leukemia and lymphomas. The fact that the deficits between white and black patients with leukemia and lymphoma have been overcome for pediatric patients in the United States indicates that this can also be achieved in young adults and older adolescents. A major solution would be access to clinical trials through COG or other clinical trials for the next older age group. The current National Cancer Institute Progress Review Group offers recommendations that are relevant to these disparate outcomes observed in this study; these will be reviewed. [Display omitted]

Development and Evaluation of a Culturally Tailored Educational Video: Changing Breast Cancer–Related Behaviors in Chinese Women

This study developed and evaluated a culturally tailored video guided by the health belief model to improve Chinese women's low rate of mammography use. Focus-group discussions and an advisory board meeting guided the video development. A 17-min video, including a soap opera and physician-recommendation segment, was made in Chinese languages. A pretest/posttest pilot was conducted to evaluate the efficacy of the video in changing knowledge, beliefs, and screening intentions among Chinese women (age >or= 40) who were nonadherent to current National Cancer Institute's mammography guidelines (n=52). The results showed that the video significantly increased these women's screening intentions, knowledge, perceived risk for breast cancer, and perceived benefits of mammography. Chinese immigrant women were less likely to hold an Eastern view of health care and report barriers to screening after viewing the video. This video might have the potential to increase adherence to mammography screening in Chinese women.

Prospective analysis of TEL/AML1-positive patients treated on Dana-Farber Cancer Institute Consortium Protocol 95-01

AbstractIn a retrospective analysis, we previously reported that children whose leukemia cells harbored the TEL/AML1 gene rearrangement have excellent outcomes. From 1996 to 2000, we conducted a prospective study to determine the incidence and outcomes of children with TEL/AML1-positive acute lymphoblastic leukemia (ALL). Children with newly diagnosed ALL were treated on DFCI ALL Consortium Protocol 95-01. Patients were risk stratified primarily by current National Cancer Institute (NCI)–Rome risk criteria. With a median follow-up of 5.2 years, the 5-year event-free survival for TEL/AML1-positive patients was 89% compared with 80% for TEL/AML1-negative B-precursor patients (P = .05). The 5-year overall survival rate was 97% among TEL/AML-positive patients compared with 89% among TEL/AML1-negative patients (P = .03). However, in a multivariable analysis, risk group (age and leukocyte count at diagnosis) and asparaginase treatment group, but not TEL/AML1 status, were found to be independent predictors of outcome. We conclude that TEL/AML1-positive patients have excellent outcomes, confirming our previous findings. However, factors such as age at diagnosis and presenting leukocyte count should be taken into consideration when treating this group of patients.

Fludarabine treatment of patients with chronic lymphocytic leukemia induces a p53-dependent gene expression response

AbstractFludarabine, the current standard treatment for B-cell chronic lymphocytic leukemia (CLL), can induce apoptosis in CLL cells in vitro, and a number of molecular mechanisms contribute to its cytotoxicity. Using gene expression profiling, we investigated the molecular consequences of fludarabine treatment of patients with CLL in vivo. In 7 patients with CLL, a consistent gene expression signature of in vivo fludarabine exposure was identified. Many of the fludarabine signature genes were known p53 target genes and genes involved in DNA repair. In vitro treatment of CLL cells with fludarabine induced the same set of genes as observed in vivo, and many of these genes were also induced by in vitro exposure of CLL cells to ionizing radiation. Using isogenic p53 wild-type and null lymphoblastoid cell lines, we confirmed that many of the fludarabine signature genes were also p53 target genes. Because in vivo treatment with fludarabine induces a p53-dependent gene expression response, fludarabine treatment has the potential to select p53-mutant CLL cells, which are more drug resistant and associated with an aggressive clinical course. These considerations suggest that fludarabine treatment should be given in strict accordance to the current National Cancer Institute (NCI) guidelines that have established criteria of disease activity that warrant treatment.

Prostate Cancer Chemoprevention Agent Development: The National Cancer Institute, Division of Cancer Prevention Portfolio

We describe the current National Cancer Institute chemoprevention agent development program and provide a summary of the intermediate end points used. The National Cancer Institute is currently sponsoring a wide range of studies of promising chemoprevention agents in a variety of informative cohorts, eg high grade prostatic intraepithelial neoplasia, positive family history of cancer, increased prostate specific antigen with negative biopsies, prostate cancer followed expectantly, prostate cancer awaiting definitive therapy and the general population. The rationale for each agent under investigation is derived from epidemiological observations, prostate cancer treatment trials, secondary analyses of large cancer prevention studies, an understanding of cancer biology and prostate carcinogenesis, and/or experimental animal models. Carcinogenesis is a multistep process occurring over decades which is characterized by disruption of the normal regulatory pathways controlling cellular proliferation, programmed cell death and differentiation. Administration of agents to reverse, inhibit or slow this process of malignant transformation is known as chemoprevention. Chemoprevention represents a promising approach to reducing the morbidity and mortality of prostate cancer. A variety of agents are currently being studied in phase 2 clinical trials, some of which may warrant subsequent evaluation in phase 3 trials with definitive cancer end points. Two large phase 3 trials, the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, which are ongoing, are also sponsored by the National Cancer Institute.

Chemoprevention of superficial bladder cancer.

The development, evaluation and approval of promising agents for bladder cancer prevention (chemoprevention)depends upon the rational integration of four key components: a) Agents (pharmaceuticals, biologics and nutrients); b) Biomakers (intermediate endpoints that predict for clinical response and risk reduction; c) Cohorts (well defined high risk target populations d) Designs (efficient trial designs linked to the clinical phase of development). The promise of this overall strategy is the ability to conduct faster, smaller and more cost effective trials which incorporate validated surrogate endpoints rather than conventional clinical endpoints (cancer incidence, recurrence and survival). Current National Cancer Institute (NCI) phase III bladder cancer chemopreventive trials in progress are described. Since most patients with superficial (transitional cell) bladder cancer present with early disease (Ta, T1, Tis lesions) that frequently recurs and is easily accessible by serial cystoscopy and urine cytology, bladder cancer serves as a powerful clinical for conducting prevention trials of new agents for a tobacco related malignancy.

Management of Cancer Treatment–Related Diarrhea: Issues and Therapeutic Strategies

The cancer treatment–related diarrhea caused by acute graft-versus-host disease (GVHD) and chemotherapeutic agents, particularly fluoropyrimidines and irinotecan, significantly affects patient morbidity and mortality. The mechanisms causing cancer treatment–related diarrhea are not fully understood, but histopathologic evidence points to a multifactorial process that causes an absorptive and secretory imbalance in the small bowel. Cancer treatment–related diarrhea could be life-threatening, yet assessment and treatment are not currently standardized. Several clinicians participated in a closed roundtable meeting to review the mechanisms of chemotherapy-induced diarrhea (CID) and GVHD-induced diarrhea, management issues in cancer treatment–induced diarrhea, and pharmacologic approaches to treatment. The meeting produced a proposal for new treatment guidelines and an algorithm, which include the use of octreotide for the management of CID- and GVHD-induced diarrhea. The development of diarrhea assessment guidelines that expand on the current National Cancer Institute criteria and allow for better patient management was also proposed.

The National Cance Advisory Board

The National Cance Advisory Board

Cancer Virus Redux

W hen the U.S. government declared its war on in 1971, viruses were considered to be among the most likely cancer-causing agents. The National Cancer Institute (NCI) in Bethesda, Md., had special program to screen tumor cells for the presence of virus particles, but, says current NCI head Vincent T DeVita, wasn't to be that simple. Despite expense and effort, no one was able to isolate cancer virus from human tumor cells during that initial push; there arose a lot of skepticism about viruses as cause of DeVita says today. Some researchers dropped out of the field; others shifted their emphasis to basic virology research. Out of that [shift] emerged the basic ability to isolate viruses that we didn't have in the beginning, says DeVita. We're now back in the business of finding viruses [as a] cause of he said at the recent American Cancer Society's science writers' seminar in San Diego. Researchers there described virus-cancer connections ranging from epidemiological links coincident occurrences of virus and type of cancer in given population -to direct laboratory observations of virus transforming normal cells into cancerous ones. Viruses have been fingered in liver cancer, the most common cancer in the world; cervical cancer; Burkitt's lymphoma; nasopharyngeal carcinoma; and an adult T cell leukemia. But researchers are quick to caution that though these cancers are believed to be caused by they don't spread as easily as common viruses spread -for example, with sneeze. We have not found that kind of transmission of cancer viruses, says DeVita. You need very intimate contact to spread the viruses that we know can be spread. None of it seems to be easy, thank God. Virus-associated cancers are more common in less developed nations, DeVita notes. Differences in hygiene may be one reason, he suggests, with individuals exposed at an earlier age, giving cancer viruses longer time to act. The virus-associated cancers, which tend to occur earlier in life, also wind up representing greater proportion of total cancers in these countries, possibly because people in less developed countries are more likely to die before getting the old age cancers like cancer of the urinary tract, bladder and gut wall.

Current NCI Preclinical Antitumor Screening in Vivo: Results of Tumor Panel Screening, 1976–1982, and Future Directions

This chapter discusses the current National Cancer Institute (NCI) preclinical antitumor screening in vivo. Preclinical models used by the NCI to select new drugs for clinical trial have changed periodically over the years. Changes in screening methodology have resulted from fundamental studies of biologic factors that affect the success of treatment, such as the relationship of tumor cell growth kinetics to drug responsiveness and from retrospective analyses of correlations between clinical and preclinical efficacy. The increased level of effort required to test a compound in a panel of tumors meant that the input of agents for evaluation would have to be limited. Of a number of alternatives considered, it was determined that the most reasonable approach would be to subject materials to a relatively sensitive and cost efficient in vivo prescreens-those showing a modest but reproducible.

Current National Cancer Institute Center programs. Workshop I summary.

CancerVolume 29, Issue 4 p. 906-907 ArticleFree Access Current National Cancer Institute center programs. Workshop I summary William E. Powers MD, William E. Powers MD Moderator Professor of Radiology, Washington University School of Medicine, The Edward Mallinckrodt Institute of Radiology, St. Louis, Mo.Search for more papers by this author William E. Powers MD, William E. Powers MD Moderator Professor of Radiology, Washington University School of Medicine, The Edward Mallinckrodt Institute of Radiology, St. Louis, Mo.Search for more papers by this author First published: April 1972 https://doi.org/10.1002/1097-0142(197204)29:4<906::AID-CNCR2820290432>3.0.CO;2-5 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume29, Issue4April 1972Pages 906-907 RelatedInformation

Current National Cancer Institute Center programs.

CancerVolume 29, Issue 4 p. 887-888 ArticleFree Access II. Current National Cancer Institute center programs William M. Roberson MD, William M. Roberson MD Program Director, Cancer Research Centers, Extramural Activities, National Cancer Institute, Bethesda, Md.Search for more papers by this author William M. Roberson MD, William M. Roberson MD Program Director, Cancer Research Centers, Extramural Activities, National Cancer Institute, Bethesda, Md.Search for more papers by this author First published: April 1972 https://doi.org/10.1002/1097-0142(197204)29:4<887::AID-CNCR2820290426>3.0.CO;2-N AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume29, Issue4April 1972Pages 887-888 RelatedInformation