Progress in clinical chemoprevention.
Gary J. KelloffErnest T. HawkJudith E. KarpJames A. CrowellC W BooneVernon E. SteeleRonald A. LubetCaroline C. Sigman
76
Citation
0
Reference
10
Related Paper
Citation Trend
Keywords:
Drug Development
Cancer Prevention
Cite
The term "cancer chemoprevention" refers to the prevention of cancer by intervening with drugs prior to the malignant (i.e., invasive) stage of carcinogenesis. The development of chemopreventive drugs is the major objective of the Chemoprevention Branch at the National Cancer Institute. The testing of drugs for cancer chemoprevention differs from testing of those for cancer treatment. Chemopreventive drug trials involve healthy target populations, and the endpoints of reduced cancer incidence or mortality, reduced/eliminated precancerous lesions, or increased latency must be achieved with little or no drug toxicity. The design of cancer chemoprevention trials for prostate presents several problems, such as the age of the study population and undependable methods for detecting microscopic foci by sequential sampling. A major motivation for organizing this workshop is the development of strategies for the design of chemopreventive intervention trials for prostate cancer. One of the most difficult problems of chemoprevention drug testing is the necessity of lengthy trials due to the long developmental period of many cancers. This is especially true for prostate cancer. A major solution to the problem is the use of intermediate biomarkers, defined as morphological or molecular intraepithelial changes that can constitute short-term endpoints in chemoprevention clinical trials. They are categorized as histological, genetic, proliferation-related, and differentiation-related. Modulation of intermediate biomarkers, instead of cancer incidence, as trial endpoints would allow chemoprevention trials to be of shorter duration, to use fewer subjects, and to be of lower cost. Review of the current status of prostatic intermediate biomarkers, and methods for identifying and validating them, are also major reasons for convening this workshop.
Drug Development
Cancer Prevention
Cite
Citations (20)
Research on the neurobiology of cancer, which lies at the border of neuroscience and oncology, has elucidated the mechanisms and pathways that enable the nervous system to modulate processes associated with cancer initiation and progression. This research has also shown that several drugs which modulate interactions between the nervous system and the tumor micro- and macroenvironments significantly reduced the progression of cancer in animal models. Encouraging results were also provided by prospective clinical trials investigating the effect of drugs that reduce adrenergic signaling on the course of cancer in oncological patients. Moreover, it has been shown that reducing adrenergic signaling might also reduce the incidence of cancer in animal models, as well as in humans. However, even if many experimental and clinical findings have confirmed the preventive and therapeutic potential of drugs that reduce the stimulatory effect of the nervous system on processes related to cancer initiation and progression, several questions remain unanswered. Therefore, the aim of this review is to critically evaluate the efficiency of these drugs and to discuss questions that need to be answered before their introduction into conventional cancer treatment and prevention.
Cancer Prevention
Cite
Citations (5)
A fundamental goal in molecular oncology is to unravel the underlying mechanisms which cause the cell transformation. In line with this approach, genome-wide functional screening approaches have revealed exciting insights into heterogeneous nature of cancer. Rapidly expanding horizons of research have unraveled myriad of pathways which play instrumental role in carcinogenesis and metastasis. Oxidative stress has also been reported to be significantly involved in cancer onset and progression. In line with this approach, oxidative stress modulating chemicals have always been sharply divided into antioxidants and oxidative stress-inducing agents. Conceptual and experimental advancements have enabled us to critically analyze full potential of these two different groups of chemicals in cancer chemoprevention. Different antioxidants are currently being analyzed in different phases of clinical trials. Although it has been reported in the literature that antioxidant supplements reduce tumor cells in some tumors or cause volume reduction in solid tumor sizes, there is no definite consensus. Therefore, an antioxidant supplement guideline based on more detailed clinical research and as a result of these is needed to achieve the best care for cancer patients and to avoid risky treatments for cancer patients.
Cite
Citations (4)
Drug repositioning
Repurposing
Cancer drugs
Drug Development
Cite
Citations (302)
Head and neck squamous cell carcinoma (HNSCC) is one of the most fatal cancers worldwide. Despite advances in the management of HNSCC, the overall survival for patients has not improved significantly due to advanced stages at diagnosis, high recurrence rate after surgical removal, and second primary tumor development, which underscore the importance of novel strategies for cancer prevention. Cancer chemoprevention, the use of natural or synthetic compounds to prevent, arrest, or reverse the process of carcinogenesis at its earliest stages, aims to reverse premalignancies and prevent second primary tumors. Genomics and proteomics information including initial mutation, cancer promotion, progression, and susceptibility has brought molecularly targeted therapies for drug development. The development of preventive approaches using specific natural or synthetic compounds, or both, requires a depth of understanding of the cross-talk between cancer signaling pathways and networks to retain or enhance chemopreventive activity while reducing known toxic effects. Many natural dietary compounds have been identified with multiple molecular targets, effective in the prevention and treatment of cancer. This review describes recent advances in the understanding of the complex signaling networks driving cancer progression and of molecularly targeted natural compounds under preclinical and clinical investigation.
Drug Development
Cancer Prevention
Cite
Citations (64)
Strategies for the treatment of cancer remain unsatisfactory due to the poor understanding of the complicated underlying molecular mechanisms of carcinogenesis. A number of types of cancer exhibit a marked association with dietary habits and lifestyles. Therefore, the modulation of dietary habits or lifestyles may be an effective strategy for preventing the formation and progression of cancer. Proteins and polypeptides from soybean have been developed as healthcare products due to their marked activity in inhibiting the progression of cancer at various stages. Lunasin, containing 43 amino acid residues, is one such example of a soybean‑derived polypeptide that has been demonstrated to exhibit marked anti-cancer activity. In the present review, studies of the underlying molecular mechanisms and potential advantages of lunasin in the prevention and treatment of cancer have been examined, to provide a theoretical reference for the development of natural product‑based agents or healthcare products for the prevention and treatment of cancer.
Cancer Prevention
Cite
Citations (36)
Targeting Epigenetics for Cancer Prevention By Dietary Cancer Preventive Compounds—The Case of miRNA
In cancer, genetic mutations have long been considered to be the only driver of neoplasia. However, there is increasing evidence that epigenetic alterations could also play a major role in carcinogenesis and cancer. A number of experimental and epidemiologic studies have shown that many classes of dietary phytochemicals possess cancer-preventive and epigenetic-modifying properties. The report by Derry and colleagues in this issue of the journal shows that grape seed extract (GSE) prevents azoxymethane (AOM)-induced colon colitis via epigenetic microRNA (miRNA) regulation. Although the precise mechanism underlying the control of miRNA expression is not well understood currently, epigenetic changes could play a major role. This report, along with increasing evidence showing the impact of dietary phytochemicals on epigenetic activities, offers new perspectives on miRNA and epigenetic regulation in cancer prevention.
Cancer Prevention
Cite
Citations (12)
In 2012, a total of 1,638,910 new cases and 577,190 deaths from cancer are projected to occur in the United States [1]. From 2004 to 2008, the overall cancer death rate was decreased by 1.8% in men versus 1.6% in women yearly, which may result from the successful implementation of early detection, treatment, and prevention methods [1]. Although its potential has not yet been fully realized, chemoprevention by using pharmaceuticals (e.g. anti-inflammatory drugs) to retard or reverse the process of carcinogenesis and progression of cancer has been recognized to benefit individuals with precancerous lesions or with genetic susceptibility to cancer [2-4]. The concept of chemoprevention encompasses all stages of disease progression including the prevention of tumor initiation through DNA repair, detoxification, free-radical scavenging, and carcinogen metabolism; prevention of tumor promotion by inhibiting proliferation or inducing differentiation or apoptosis; and the inhibition of tumor progression by suppressing tumor cell invasion and metastasis [5].
Omics
Cite
Citations (9)
Cite
Citations (1)
Chemoprevention is the administration of agents (drugs, biologics, dietary supplements, or nutrients) to reduce the risk of developing cancer or prevent the recurrence of cancer. The National Cancer Institute, Division of Cancer Prevention (NCI, DCP), is a major sponsor of cancer preventive preclinical and clinical research. As such, it has developed a comprehensive drug development program specifically designed to meet the requirements needed for cancer preventive drugs to achieve initial regulatory approval. Clinical development of cancer prevention agents presents unique challenges that are not encountered with most cancer therapeutic agents. To meet these challenges, NCI, DCP has implemented new approaches and programs, including phase 0 clinical trial designs and microdose studies. In addition, the PREVENT Cancer Program was recently implemented by NCI, DCP to offer a formalized structure for moving drugs forward in the prevention pipeline using a continue/not continue decision process. Likewise, DCP has implemented a Clinical Trials Consortium to further develop these agents. These and other approaches will be discussed in this commentary.
Cancer Prevention
Drug Development
Cite
Citations (6)